斯芬克斯猫皮肤的组织学和皮肤镜学的描述

王帆

Histological and dermatoscopic description of sphynx cat skin

斯芬克斯猫皮肤的组织学和皮肤镜学的描述

作者：David W. Genovese, Tammy L. Johnson, Ken E. Lamb and Wallace D. Gram

翻译：许晓鸥

abstract

Background -Histological and hair coat abnormalities of the alopecic sphynx cat have not been described in detail. The hairless allele (hr) in sphynx cats represents a mutation in the gene for keratin 71, a protein expressed in the inner root sheath of humans and mice.

Hypothesis/Objectives -To describe the histological and dermatoscopic abnormalities of sphynx cat skin.

Animals-Skin biopsies were collected from 14 sphynx cats and five cats with normal coats. Dermatoscopic examinations were performed on 11 sphynx cats and six additional control cats.

Methods - Vertical and horizontal sections of skin biopsy samples from sphynx and control cats were reviewed. Dermatoscopic images were compared between sphynx and control cats.

Results - Sphynx cat hair follicles were often small, curved and kinked and demonstrated infundibular hyperkeratosis and dilatation. Changes in the inner root sheath of sphynx cats included a poorly defined Henle’s layer in addition to vacuolar-like changes and eosinophilic globules in Huxley’s layer. Dermal papillae in sphynx cat anagen bulbs lacked the normal flame shape and were surrounded by epithelial cells arranged in a disorderly manner. The degree of follicular abnormalities varied between follicles. Follicular density was similar for both sphynx cats and control animals. Sphynx cat hair shafts were misshapen, smaller in diameter and rarely medullated. Dermatoscopy revealed similar hair coat density in sphynx and control cats.

Conclusions and clinical importance - Sphynx cats demonstrated hair follicle dysplasia, with abnormal shaft production but without a decrease in follicle quantity. Abnormalities in sphynx cat follicles are similar to those inmurine KRT71 mutants and suggest abnormal hair shaft keratinization.

摘要

背景-斯芬克斯无毛猫的组织学和毛发异常没有被详细研究过。斯芬克斯猫少毛等位基因（hr）在角蛋白71基因上产生突变，角蛋白71为人和小鼠根鞘内表达的一种蛋白质。

假设/目的-描述斯芬克斯猫组织学和皮肤镜的异常情况。

动物-从14只斯芬克斯猫和5只普通猫身上取皮肤活组织样本。皮肤镜检查11只斯芬克斯猫和6只对照猫。

方法-分别观察斯芬克斯猫和普通猫皮肤活组织样本的垂直面和水平面。相互比较两者的切面图像。

结果-斯芬克斯猫毛囊通常小、弯而扭结，并可见漏斗部过度角化和扩张。斯芬克斯猫根鞘内部变化包括缺乏明确的Henle's层，另外Huxley's层出现空泡样变化和嗜酸性颗粒。斯芬克斯猎生长期毛根真皮层的乳头状突起缺乏正常的火焰状，并围绕着无序排列的上皮细胞。毛囊畸形程度不一。斯芬克斯猫和普通猫的毛囊密度相同。斯芬克斯猫毛干畸形，直径小并且很少有毛髓。皮血管经检查显示斯芬克斯猫和对照组毛发密度相同。

总结与临床意义-斯芬克斯猫毛囊发育异常，缺乏毛干产物，但毛囊量未见减少。斯芬克斯猫毛囊畸形跟鼠KRT7I突变体一致，并显示毛干角化异常

 

Introduction

介绍

The term ‘alopecia’ can be used to indicate a decrease in the number, length or diameter of hair shafts. Congenital alopecia in domestic animals is caused by a reduction in hair follicle quantity or quality, with the latter divided into the following two arbitrary categories: hair follicle dysplasia caused by defects in follicular development with morphological abnormalities and hair follicle dysplasia with defects in shaft formation where the follicles appear normal. The sphynx (Canadian sphynx) cat is a congenitally alopecic breed that originated in Canada in the 1960s. Sphynx cats are not completely hairless and have been described as having few, fine, down-like hairs, with tufts of hair located on the ears, muzzle, tail, feet and scrotum and with oily or greasy skin. They are more likely than most other cat breeds to harbour cutaneous Malassezia species of yeast. The Devon rex-breed was used in perpetuating the sphynx-breed, and a very close genetic relationship exists between the two breeds.

术语“脱毛”可用于表示毛干的数量、长度或直径减少。动物先天性脱毛是由于毛囊数量或质量减少，后者分为以下两个任意类别：毛囊发育缺陷伴形态学异常的毛囊发育异常和毛干形成缺陷伴毛囊外观正常的毛囊发育异常。斯芬克斯（加拿大斯芬克斯）猫是20世纪60年代起源于加拿大的先天性脱毛品种。斯芬克斯猫并不完全无毛并被描述为毛发很少、细小、仿羽状毛，伴簇状毛，位于耳部、嘴周、尾部、足部和阴囊皮肤，且拥有油性或油腻的皮肤。它们比大多数其他猫品种更容易携带皮肤马拉色酵母菌。德文卷毛猫保有斯芬克斯品种血统，两个品种之间存在非常密切的基因关系。

 

The sphynx hairless allele (hr) is autosomal recessive and represents a mutation in the keratin 71 gene, KRT71. Keratin 71 is a type II keratin expressed through-out the inner root sheath (IRS) in mice and humans;the location of keratin 71 protein expression has not been confirmed in cats. The IRS is vital in moulding the hair shaft,  and mutations in KRT71 have been associated with abnormal hair shafts as well as histological abnormalities including an abnormal IRS and curved/twisted hair follicles. Mutations in KRT71 have also been identified in dogs, mice, rats and humans.

斯芬克斯猫无毛等位基因(hr)是常染色体隐性遗传，代表角蛋白71基因KRT71的突变。角蛋白71是一种在小鼠和人类中通过内根鞘(IRS)表达的II型角蛋白；角蛋白71蛋白表达的位置尚未在猫中得到证实。IRS在毛干塑形中至关重要，KRT71突变与毛干异常以及组织学异常相关，包括IRS异常和毛囊弯曲/扭曲。在犬、小鼠、大鼠和人类中也发现了KRT71突变。

 

The authors are unaware, to the best of their knowledge, of previous prospective studies that have described sphynx cat skin histologically, although there are reports presenting histological findings from the occasional sphynx cat skin sample presented to diagnostic laboratories. These findings included small and curved follicles that were mostly in anagen, with hair shafts of decreased diameter that were noted rarely to penetrate the epidermis. Authors of an earlier study reported hairs of abnormal diameter that lacked a well-formed bulb on trichoscopic evaluation in the sphynx cat. The goals of the present study were to systematically to describe the histological abnormalities of sphynx cat skin and to report dermatoscopic findings of sphynx cats.

据作者所知，虽然他们不知道以前的前瞻性研究已经从组织学上描述了斯芬克斯猫的皮肤，但有从偶然提交到诊断实验室的斯芬克斯猫皮肤样本的组织学结果的报道。这些结果包括主要在生长期的小而弯曲的毛囊，以及很少观察到穿透表皮的直径减小的毛干。早期研究的作者报告了斯芬克斯猫的毛发直径异常，在显微镜检查中缺乏发育良好的毛球。本研究的目的是系统地描述斯芬克斯猫皮肤的组织学异常，并报告斯芬克斯猫的皮肤镜结果。

 

Materials and methods

材料与方法

All cats were client owned, and informed owner consent was obtained prior to any procedures. All procedures were performed solely as part of this investigation. Skin biopsy samples were collected from the lateral or dorsolateral thorax of 14 sphynx cats using a 6 mm biopsy punch instrument. From six of the 14 sphynx cats, samples were also collected from other sites, namely lumbar skin (five cats), leg (one cat) and pinnae (one cat). Local anaesthesia (lidocaine hydrochloride; Med-Pharmex, Pomona, CA, USA) was used in all cats except for one cat that was euthanized (for unrelated reasons)immediately prior to sample collection. If necessary, sedation was carried out with either dexmedetomidine (Dexdomitor; Orion Corporation, Espoo, Finland) or a combination of diazepam (Diazepam; Hospira, Lake Forest, IL, USA) and ketamine (Ketathesia; Butler Animal Health Supply, Dublin, OH, USA). Skin biopsy samples were collected from the lateral thorax of five domestic short hair cats with grossly normal coats that were euthanized for reasons unrelated to the skin. Wedge biopsies were taken from two of these cats, and a 6 mm skin biopsy punch was used in the other three cats. Dermatological examinations were performed on 13 of the 14 sphynx cats.

所有猫均为家养猫，在任何操作前均获得主人的知情同意书。调查中的所有外科手术操作仅进行一次。使用6 mm活检打孔器从14只斯芬克斯猫的外侧或胸部背外侧采集皮肤活检样本。14只斯芬克斯猫中的6只，还从其他部位采集了样本，即腰部皮肤（5只猫）、腿部（1只猫）和耳廓（1只猫）。除1只猫在采样前即时进行了安乐死（出于不相关原因）外，所有猫均使用局部麻醉（盐酸利多卡因）。必要时，使用右美托咪定或地西泮（地西泮）和氯胺酮联合给药进行镇静。从5只被毛基本正常的家养短毛猫的侧胸皮肤采集活检样本，这些猫因与皮肤无关的原因被安乐死。其中2只猫进行楔形取样，另外3只猫采用6 mm皮肤活检打孔器采样。对14只斯芬克斯猫中的13只进行了皮肤镜检查。

 

Tissues were fixed in 10% neutral buffered formalin. They were trimmed, processed and embedded in paraffin, sectioned at 5 μm and stained with haematoxylin and eosin. Whole slide images were created with Philips Ultra Fast Scanner (Royal Phillips, the Netherlands) and viewed with Philips Image Management System (IMS) for automated digital slides (version 2.2.1.2; Royal Phillips). Scanned images were viewable from 1 to 100 digital zoom. All measurements were made with IMS embedded measurement tools. The only exception was one of the horizontal sections from a control cat, which was viewed using the eSlideShare online viewing system (Aperio; Leica Biosystems, Wetzlar, Germany). For the control cats whose samples were collected via wedge biopsy, a section similar in size to the 6 mm punch biopsy with proper orientation was chosen for evaluation. Anagen bulb width measurements were taken from the lateral thorax or dorsolateral thorax in the vertical (transverse) section (range of four to 20 anagen bulbs counted per cat). The diameter of 100 hair shafts was measured using horizontal sections. All hair shafts were measured from a follicle group before moving on to another follicle group, and this was continued until 100 shaft diameters had been measured. The presence or absence of a medulla was noted for each hair shaft counted.

将组织在10%中性福尔马林中固定，修剪处理后并进行石蜡包埋，进行5 μm切片并用苏木精和伊红染色。使用Philips Ultra快速扫描仪创建全切片图像，并使用Philips图像管理系统(IMS)查看自动数字切片。扫描图像可从1倍到100倍数字变焦查看。所有测量均使用IMS嵌入式测量工具进行。唯一的例外是对照猫的水平部分之一，使用eSlideShare在线查看系统查看。对于通过楔形活检采集样本的对照猫，选择大小与正确定向的6 mm钻取活检相似的切片进行评价。在垂直（横向）切片中，从外侧胸部或背外侧胸部进行生长期毛球宽度测量（每只猫计数4-20个生长期毛球的范围）。采用水平切面测量100个毛干的直径。在移至另一个毛囊组之前，测量毛囊组的所有毛干，并持续至测量100个毛干直径。对于计数的每个毛干，记录是否存在髓质。

 

The hair follicle cycle stage was determined for over 100 follicles for each cat (range 101-120) in a horizontal section below the level of the isthmus. Only anagen and telogen follicles were included. Anagen follicles were characterized by the presence of an IRS and telogen follicles by trichilemmal keratinization; telogen follicles were further characterized as haired telogen or kenogen (hairless telogen). The number of follicles per follicle group was also noted in a horizontal section (range of 10-23 follicle groups counted per cat). In order to calculate follicular density, all follicles within a defined area of the histological section were counted in a horizontal section (follicular density = number of hair follicles in histological section/area of histological section).

在峡部水平以下的水平切片中，确定每只猫超过100个毛囊（范围101-120）的毛囊周期阶段。仅包括生长期和休止期毛囊。生长期毛囊的特征是存在IRS和通过毛膜角化的休止期毛囊；休止期毛囊进一步的特征是有毛休止期或kenogen（无毛休止期）。在水平切片中也记录了每个毛囊组的毛囊数量（每只猫计数10-23个毛囊组的范围）。为了计算毛囊密度，在水平切片中对组织切片规定区域内的所有毛囊进行计数（毛囊密度 = 组织切片中的毛囊数量/组织切片面积）。

 

Dermatoscopic examinations were performed on 11 of the 14 sphynx cats enrolled and also on six control cats with normal coats (these were different from the control cats that had skin biopsies collected). Prior to evaluation, the control cats had their hair clipped with a 0.25 mm clipper blade. The sphynx cats were not clipped prior to dermatoscopic examination. The images were taken with a digital dermatoscope (Firefly DE300; FireflyGlobal, Belmont, MA, USA) and viewed on a computer screen via a USB connection and software programme (FireFlyPro; FireflyGlobal).

对入组的14只斯芬克斯猫中的11只以及6只被毛正常的对照猫（与采集皮肤活检的对照猫不同）进行了皮肤镜检查。评价前，用0.25 mm剪毛器剃除对照猫的被毛。在皮肤镜检查前未对斯芬克斯猫剃毛。使用电子皮肤镜(Firefly DE300；FireflyGlobal，Belmont，MA，USA)拍摄图像，并通过USB连接和软件程序(FireFlyPro；FireflyGlobal)在计算机屏幕上查看。

 

Statistical analysis

统计学分析

Error residuals were analysed and deemed normally distributed (Shapiro-Wilks test). To accommodate for the subject measurement variation when multiple measurements per subject were recorded, a nested effect ANOVA (subject within group) was performed when appropriate. The nested effect ANOVA treated subject as a random effect to determine mean differences between sphynx and control cats. Post hoc mean differences were established using Tukey’s adjustment. All analyses were considered significant at P < 0.05 and were carried out using SAS 9.3 (SAS Institute Inc., Cary, NC, USA).

分析误差残差并认为其呈正态分布（Shapiro-Wilks检验）。为适应每例受试者多次测量时的受试者测量变异，适当时进行嵌套效应ANOVA（组内受试者）。巢式效应ANOVA将受试者视为随机效应，以确定斯芬克斯猫和对照猫之间的平均差异。使用Tukey调整确定事后平均差异。认为所有分析均具有显著性(P < 0.05)，并使用SAS 9.3(SAS Institute Inc.,Cary,NC,USA)进行。

 

Results

结果

Animals

动物

Sphynx cats

斯芬克斯猫

Seven of the 14 sphynx cats were male (two intact) and seven female (two intact). Ages ranged from 6 months to 11 years, with a mean age of 4.3 years (median 4 years). Vertical or transverse sections (used for anagen bulb width measurements) were available for 13 of the 14 sphynx cats [seven female (two intact) and six male (two intact); mean age of 3.6 years], while horizontal sections were available for eight [five female (two intact) and three male neutered; mean age of 4.3 years]. The mean age of the 11 sphynx cats [six females (two intact) and five neutered males] used for dermatoscopy was 4.5 years (range 2-10 years; median 3 years).

14只斯芬克斯猫中的7只为雄性（2只未去势），7只为雌性（2只未绝育）。年龄范围为6个月至11岁，平均年龄为4.3岁（中位年龄4岁）。14只斯芬克斯猫中有13只[7只雌性（2只未绝育）和6只雄性（2只未去势）；平均年龄3.6岁]可获得垂直或横切面（用于生长期毛球宽度测量），而8只[5只雌性（2只未绝育）和3只去势雄性；平均年龄4.3岁]可获得水平切面。用于皮肤镜检查的11只斯芬克斯猫[6只雌性（2只未绝育）和5只去势雄性]的平均年龄为4.5岁（范围2-10岁；中位数3岁）。

 

All sphynx cats had no gross dermatological lesions at the biopsy sites except for diffuse alopecia. Fine, short hairs were visible with unaided vision at most normally haired body sites. Most hairs were very short, but typically longest on the muzzle, ears and tail, where they approached a length of 1 cm in some cats. Whiskers were sparse, short and fine when present. Eye-lashes were not seen in any sphynx cats. Brown adherent debris was visible on the skin and nails, except on cats that had been bathed recently. The debris was often fine and diffuse, but larger clumps (up to~2-3 mm) were also present.

除弥漫性脱毛外，所有斯芬克斯猫活检部位均无皮肤病变。在大多数正常毛发的身体部位，肉眼可见细短毛发。大多数毛发非常短，但通常在鼻口部、耳朵和尾部最长，在一些猫中接近1 cm的长度。胡须稀疏，短而细。在任何斯芬克斯猫中均未观察到眼睫毛。皮肤和指甲上可见棕色粘附碎片，最近洗澡的猫除外。碎片通常较细且弥散，但也存在较大的团块（高达~2-3 mm）。

 

Control cats

对照组猫

Five control cats were used for skin biopsy samples from the lateral thorax and six different cats were used as controls for dermatoscopic examinations. Four of the five control cats used for biopsy samples were neutered males and the other was a spayed female. The average age was 8 years (range 5-12 years; median 7 years). Vertical or transverse sections (used for anagen bulb measurements) were available for three control cats [ages 5(spayed female), 7 (spayed female) and 12 years (spayed female)], while horizontal sections were also available for three cats (all neutered males; ages 5, 6 and 9 years). Amongst the six cats used as controls for the dermatoscopic examinations, four were spayed females and two neutered males. The age range for these six cats was 13 months to 8 years, with a mean age of 4.2 years (median 4 years). Skin lesions were absent in all control cats.

5只对照猫用于侧胸皮肤活检标本，6只不同猫作为皮肤镜检查的对照。用于活检样本的5只对照猫中有4只为已去势雄性，另一只为已绝育雌性。平均年龄为8岁（范围5-12岁；中位年龄7岁）。3只对照猫[5岁（已绝育雌性）、7岁（已绝育雌性）和12岁（已绝育雌性）]可获得垂直或横切面（用于生长期毛球测量），而3只猫（均为已去势雄性；5、6和9岁）也可获得水平切面。在用作皮肤镜检查对照的6只猫中，4只为已绝育雌性，2只为已去势雄性。这6只猫的年龄范围为13个月至8岁，平均年龄为4.2岁（中位年龄为4岁）。所有对照猫中均不存在皮肤病变。

 

Histological findings from 14 sphynx cats

14只斯芬克斯猫的组织病理学结果

Histological findings for all sphynx cats were similar at all sites, with the exception of mild perivascular inflammation that was present in the thoracic samples from two cats. The inflammation was lymphocytic and mastocytic in one cat, while it was lymphocytic, mastocytic and eosinophilic in the other. The inflammation did not affect analysis of adnexal structures.

除2只猫的胸部样本中存在轻度血管周炎外，所有斯芬克斯猫在所有部位的组织学结果均相似。一只猫为淋巴细胞性和肥大细胞性炎症反应，而另一只猫为淋巴细胞性、肥大细胞性和嗜酸性粒细胞炎症反应。炎症不影响附件结构的分析。

 

Epidermis

表皮层

Epidermal changes were mild, with some sphynx cats exhibiting regional epidermal hyperplasia (up to six layers thick) and orthokeratotic hyperkeratosis.

表皮层变化为轻度，一些斯芬克斯猫表现出局部表皮增生（多达6层厚）和正角化性角化过度。

 

Hair follicles

毛囊

Sphynx cats had a compound follicular arrangement comparable to control cats, with a central primary follicle, lateral primary follicles and secondary follicles (Figure 1). Follicular density appeared similar to normal cats, subjectively (see below for quantification of follicular density). Normal follicular arrangement, with a bulb, isthmus and infundibulum, was maintained in the sphynx cats. At low-magnification, abnormalities appeared mild, though a decrease in follicular profile size and abnormal follicular shape could sometimes be appreciated. Sphynx follicles were often bent (Figure 2), curved (Figure 3) and occasionally followed a tortuous path, with multiple changes in direction (Figure 3). The degree of curvature and bending varied between follicles. Some follicles appeared normal and others exhibited severe abnormalities.Subjectively, many follicles appeared decreased in size (Figure 2).

斯芬克斯猫具有与对照猫相同的复合毛囊排列，具有中央初级毛囊，外侧初级毛囊和次级毛囊（图1）。毛囊密度主观上与正常猫相似（毛囊密度定量见下文）。斯芬克斯猫维持正常的毛囊结构，有球部、峡部和漏斗部。在低倍镜下，异常表现为轻度，但有时可观察到毛囊轮廓缩小和毛囊形状异常。斯芬克斯猫毛囊常变形（图2）、弯曲（图3），偶尔呈现迂回形态，方向有多处改变（图3）。毛囊之间的弯曲和变形程度不同。一些毛囊显示正常，其他毛囊显示重度异常。主观上出现许多毛囊体积缩小（图2）。

 

The IRSs of sphynx cats were more abundant than those of control cats and of nonuniform width. Variable and occasionally pronounced clear to pale basophilic vacuolar type changes and irregularly shaped eosinophilic globular foci were present in Huxley’s layer (Figures 4 and 5). The latter had similar tinctorial staining qualities, but were significantly larger than the trichohyalin granules present in the normal cats (some normal trichohyalin granules were also seen in the sphynx cats). Henle’s layer of the sphynx IRS was not as well defined as it was in the control cats (Figures 4 and 5). Anagen bulbs were decreased in size in sphynx cats (see below for anagen bulb width measurements). There was a loss of the normal flame-shaped dermal papillae in the sphynx cat anagen bulbs as well as a loss of the orderly columnar epithelial cell arrangement surrounding the dermal papillae (Figure 6). There was a relative increase in dermal papillae cellularity, with a corresponding loss in relative size of the extracellular matrix. The severities of IRS and anagen bulb abnormalities varied between individual follicles but were almost uniformly present. Infundibular dilatation was commonly present and accompanied by moderate infundibular hyperkeratosis.

斯芬克斯猫的IRSs比对照猫更丰富，宽度不均匀。赫胥黎氏（Huxley）层中存在不同且偶尔明显的透明至淡嗜碱性空泡样病变和形状不规则的嗜酸性细胞视野（图4和图5）。后者具有相似的着色染色质量，但显著大于正常猫中存在的毛透明蛋白颗粒（在斯芬克斯猫中也观察到一些正常的毛透明蛋白颗粒）。斯芬克斯猫 IRS的亨勒（Henle）层不如对照猫明确（图4和5）。斯芬克斯猫的生长期毛球尺寸减小（生长期毛球宽度测量见下文）。斯芬克斯猫生长期毛球中正常的火焰状真皮乳头缺失以及真皮乳头周围有序的柱状上皮细胞结构缺失（图6）。真皮乳头细胞结构相对增加，细胞外基质相对大小相应损失。IRS和生长期毛球异常的严重程度因单个毛囊而异，但几乎一致存在。通常存在漏斗部扩张，并伴有中度漏斗部角化过度。

 

Hair shafts

毛干

Hair shafts were present in most follicular lumens [though in sphynx cats hairless telogen (kenogen) was more prevalent; see below] and infundibula, but were small and often misshapen, with curves and bends, often undulating and wavy, with nonuniform diameter. In cross-section, hair shafts often exhibited ‘jagged’ edges rather than a round or oval outline. Hair shafts were sometimes abnormally oriented within the hair follicle. Subjectively, there was a decrease in the number of medullated hair shafts in sphynx cats compared with normal cats (see below for measured percentages of medullated hairs).

毛干存在于大多数毛囊腔[尽管在斯芬克斯猫中无毛休止期(kenogen)更普遍；见下文]和漏斗部中，但较小且通常畸形，呈现弯曲和变形，通常呈波浪状和波纹，直径不均匀。在横截面上，毛干通常表现出“锯齿状”边缘，而不是圆形或椭圆形轮廓。毛干有时在毛囊内方向异常。主观上，与正常猫相比，斯芬克斯猫的髓质毛干数量减少（髓质毛的测量百分比见下文）。

 

Sebaceous glands, sweat glands and arrector pili muscles 

皮脂腺、汗腺和立毛肌

 

No significant abnormalities were noted in sweat glands, arrector pili muscles or sebaceous glands.

在汗腺、立毛肌或皮脂腺中未观察到显著异常。

 

Histological findings from five cats with normal coat

5只猫的组织学结果具有正常被毛

No histological abnormalities were noted.

未观察到组织学异常。

 

Anagen bulb width measurements

生长期毛球宽度测量

Anagen bulb diameter measurements were significantly decreased (P < 0.0001) for sphynx cats (n = 13) when compared with the three control cats. Least-squares mean diameters were 58.87 and 74.58 μm, respectively.

与3只对照猫相比，斯芬克斯猫(n = 13)的生长期毛球直径测量值显著降低(P < 0.0001)。最小平方平均直径分别为58.87和74.58 μm。

 

Hair shaft diameter measurements

毛干直径测量

Hair shaft diameter measurements were significantly decreased (P < 0.0006) for sphynx cats (n = 8) when compared with control cats (n = 3). Least-squares mean diameters were 14.86 and 19.27 μm, respectively.

与对照猫(n = 3)相比，斯芬克斯猫(n = 8)的毛干直径测量值显著降低(P < 0.0006)。最小平方平均直径分别为14.86和19.27 μm。

 

Medullated hair shafts

有髓质毛干

The percentage of hair shafts that were medullated was significantly lower (P < 0.0001) for sphynx cats (n = 8) compared with control cats (n = 3). Percentages of hair shafts that were medullated were 3.7 and 39%, respectively.

与对照猫(n = 3)相比，斯芬克斯猫(n = 8)的有髓质毛干百分比显著较低(P < 0.0001)。有髓质毛干百分比分别为3.7%和39%。

 

Anagen and telogen follicles

生长期和休止期毛囊

The mean percentage of anagen follicles was significantly greater (P < 0.0001) and mean percentage of telogen [haired telogen plus kenogen (hairless telogen)] follicles significantly lower (P < 0.0001) in sphynx cats (n = 8) compared with control cats (n = 3). For sphynx cats, 76.89% was the mean percentage of follicles in anagen and 23.11% the mean percentage in telogen compared with 34.88 and 65.12%, respectively, for control cats. Sphynx cats had a significantly greater (P < 0.0001) mean percentage of telogen hairs that were in kenogen compared with control cats; mean percentages in kenogen were 60.07 and 11.21%, respectively.

与对照猫(n = 3)相比，斯芬克斯猫(n = 8)的生长期毛囊平均百分比显著较高(P < 0.0001)，休止期[有毛休止期加kenogen（无毛休止期）]毛囊平均百分比显著较低(P < 0.0001)。对于斯芬克斯猫，76.89%是生长期毛囊的平均百分比，23.11%是休止期毛囊的平均百分比，而对照猫分别为34.88%和65.12%。与对照猫相比，斯芬克斯猫处于无毛休止期的休止期毛发平均百分比显著更高(P < 0.0001)；无毛休止期的平均百分比分别为60.07和11.21%。

 

Follicle group size

毛囊组大小

The number of follicles per follicle group was not signifi-cantly different (P = 0.9114) between sphynx cats (n = 8) and control cats (n = 3). The least-squares mean number of follicles per group was 17.90 and 17.68, respectively.

斯芬克斯猫(n = 8)和对照猫(n = 3)之间每个毛囊组的毛囊数量无显著差异(P = 0.9114)。每组毛囊的最小平方平均值分别为17.90和17.68。

 

Hair follicle density measurements

毛囊密度测量

Hair follicle density was not significantly different (P = 0.4658) between sphynx cats (n = 8) and control cats (n = 3). The least-squares mean density was 71.83 and 80.91 follicles mm-2, respectively.

毛囊密度在斯芬克斯猫(n = 8)和对照猫(n = 3)之间无显著差异(P = 0.4658)。最小平方平均密度分别为71.83和80.91个毛囊mm-2。

 

Dermatoscopic examinations

皮肤镜检查

Many sphynx hairs were clearly seen protruding from follicular ostia and were reduced in diameter compared with control cats (Figure 7). Sphynx hairs were often curved, and kinks could occasionally be seen (Figure 7). Individual hairs could not be counted and thus numerical hair coat density was not assessed. However, coat density appeared similar for sphynx and control cats (Figure 7).

与对照猫相比，可清楚地观察到许多斯芬克斯猫毛发从毛囊口突出，且直径减小（图7）。斯芬克斯猫毛发常弯曲，偶可见到蜷缩（图7）。单个毛发无法计数，因此未评估毛发密度数值。然而，斯芬克斯猫和对照猫的被毛密度似乎相似（图7）。

 

Discussion

讨论

To the best of the authors’ knowledge, this is the first study to describe the histology of the alopecic sphynx cat systematically. Sphynx cats were shown to have compound follicle groups similar to normal cats with a similar number of follicles per group. Consistent with the limited descriptions of sphynx cat skin biopsies submitted to diagnostic laboratories, small, curved, bent follicles and hair shafts of decreased diameter were found in our study. The presence of small, abnormal anagen bulbs as also consistent with a prior study that identified poorly formed anagen bulbs on trichoscopic evaluation in sphynx cats, though our present study was better able to characterize the anagen bulb abnormalities.

据作者所知，这是首次系统地描述斯芬克斯无毛猫的组织学的研究。斯芬克斯猫显示具有与正常猫相似的复合毛囊组，每组毛囊数量相似。与提交给诊断实验室的斯芬克斯猫皮肤活检的有限描述一致，在我们的研究中发现了小的、弯曲的、变形的毛囊和直径减小的毛干。小的、异常的生长期毛球的存在也与先前的研究一致，在斯芬克斯猫的显微镜检测中发现了形成不良的生长期毛球，但我们目前的研究能够更好地描述生长期毛球异常的特征。

 

Previous reports suggesting that sphynx follicles may rarely penetrate the epidermis and that most follicular infundibula are empty differ from our findings. Previous anecdotal reports that sphynx cat skin is often covered with brown adherent debris were confirmed in this study. Further studies would be needed to identify the composition of this material. Our study expanded on the hair shaft abnormalities previously identified in sphynx cats and confirmed decreased diameter and a decreased number of medullated hair shafts. Histological hair follicle density was similar in sphynx cats compared with normal cats. Previous reporting had suggested that most sphynx follicles are in anagen, and our study confirmed a predominance of anagen follicles. Abnormalities of the IRS in sphynx cats were reported for the first time in this study.

以前的报道表明，斯芬克斯猫毛囊可能很少穿透表皮，大多数毛囊漏斗部是空的，这与我们的发现不同。本研究证实了之前的轶事报道，即斯芬克斯猫皮肤通常被棕色粘附碎片覆盖。需要进一步研究来确定该材料的组成。我们的研究扩展了以前在斯芬克斯猫中发现的毛干异常，并证实直径减小和有髓质毛干数量减少。与正常猫相比，斯芬克斯猫的组织学毛囊密度相似。以前的报道认为大多数斯芬克斯猫毛囊处于生长期，我们的研究证实生长期毛囊占优势。本研究首次报道了斯芬克斯猫IRS的异常。

 

While hair coat density appeared similar between sphynx and normal cats, we were unable to count individual follicles on our dermatoscopic images. There was an increased percentage of follicles in kenogen in sphynx cats, and it is possible that some of the abnormal sphynx cat hair shafts did not reach the epidermis, both of which could decrease coat density. However, dermatoscopy revealed many hair shafts protruding from follicular ostia, suggesting that the hairless appearance is not due to a lack of hairs but rather to the short and fine nature of the hairs. The presence of hair shafts protruding from follicular ostia does not preclude the use of the term ‘alopecia’, which, as mentioned previously, can also be used to describe hair shafts of decreased length or diameter.

虽然斯芬克斯猫和正常猫的毛发密度似乎相似，但我们无法在我们的皮肤镜图像上计数单个毛囊。斯芬克斯猫无毛休止期毛囊百分比增加，有可能部分异常的斯芬克斯猫毛干未到达表皮，两者均可使被毛密度降低。然而，皮肤镜检查发现许多毛干从毛囊口突出，提示无毛外观不是由于缺乏毛发，而是由于毛发的短而细。毛干从毛囊口突出的存在并不阻碍使用术语“脱毛”，如前所述，也可用于描述长度或直径减小的毛干。

 

A mutation in KRT71 has been identified in other cat breeds, such as the Devon rex and Selkirk rex, whose phenotypes differ from the sphynx cat. Most of the α-helical domain, vital to dimerization of type I and type II keratins, is deleted in the sphynx mutation, resulting in a drastically altered keratin 71 protein, with complete loss of function, possibly predisposing the hair to break-age. In the Devonrex, the α-helical domain is also affected, but some function is probably retained. The Don sphynx, a Russian breed of alopecic cat with a similar phenotype to the sphynx cat, has been shown to lack a KRT7120 mutation. A mutation in LPAR6 is responsible for the abnormal coat of the Cornish rex. Histological comparisons between any of these breeds and sphynx cats have not been performed.

在其他猫品种中发现了KRT71的突变，如德文郡卷毛猫和塞尔凯克卷毛猫，其表型与斯芬克斯猫不同。在斯芬克斯猫突变中，α-螺旋结构域的大部分对I型和II型角蛋白的二聚化至关重要，该结构域被删除，导致角蛋白71蛋白发生剧烈改变，功能完全丧失，可能使毛发易断裂。在德文郡卷毛猫中，α-螺旋结构域也受到影响，但可能保留了一些功能。唐斯芬克斯猫，一种俄罗斯无毛猫品种，表型与斯芬克斯猫相似，已被证明缺乏KRT7120突变。LPAR6的突变是导致柯尼斯卷毛猫毛发异常的原因。尚未对这些品种和斯芬克斯猫进行组织学比较。

 

A KRT71 mutation is responsible for a case of autosomal dominant woolly hair in a human family. People with woolly hair syndrome are characterized by fine and curly hair on the head, but they are not as severely alopecic as sphynx cats. Abnormalities in sphynx cats parallel some of those seen in murine KRT71 mutants. Hair shafts from laboratory rodents homozygous for an autosomal dominant KRT71 mutation, Rex (Re), are decreased in diameter, and these rats are also alopecic. Histological descriptions exist for the following KRT71 mutations in mice: (Ca) Caracul, Rco3, Rco12 and Rco13, and histological similarities to sphynx cats include curved/bent follicles and IRS abnormalities, such as nonuniform diameter and areas of abnormal or incomplete staining that are likely to represent abnormal keratinization. Hair shaft changes, including curves and kinks, are also similar between the mouse mutants and sphynx cats. Of the mouse KRT71 mutants, sphynx cats may be most similar to RCO3 mutants, which also exhibit alopecia though not as extensive as sphynx cats. Recessive inheritance is exhibited by both RCO3 mice and sphynx cats, whereas the other murine KRT71 mutations are dominant. The mutation in RCO3 mice results in complete absence of the α-helical domain, and the sphynx KRT71 mutation also deletes most of the α-helical domain, which is likely to result in abnormal/incomplete IRS keratinization.

KRT71突变是导致一个人类家族中一例常染色体显性遗传毛发的原因。羊毛状综合征患者的特征是头部毛发细密、卷曲，但脱发不如斯芬克斯猫严重。斯芬克斯猫的异常与鼠KRT71突变体中观察到的一些异常平行。来自常染色体显性KRT71突变纯合子Rex(Re)的实验室啮齿类动物的毛干直径减小，这些大鼠也是脱毛的。在小鼠中存在以下KRT71突变的组织学描述：(Ca)Caracul、Rco3、Rco12和Rco13，与斯芬克斯猫的组织学相似性包括弯曲/变形的毛囊和IRS异常，例如不均匀的直径和异常或内部染色区域，可能代表异常角化过程。小鼠突变体和斯芬克斯猫的毛干变化（包括弯曲和蜷缩）也相似。在小鼠KRT71突变体中，斯芬克斯猫可能与RCO3突变体最相似，RCO3突变体也表现出脱毛，但不如斯芬克斯猫广泛。RCO3小鼠和斯芬克斯猫均表现出隐性遗传，而其他鼠KRT71突变为显性遗传。RCO3小鼠的突变导致α螺旋结构域完全缺失，斯芬克斯猫KRT71突变也会删除大部分α-螺旋结构域，这很可能导致IRS角化异常/不完全。

 

The present study is limited by numerous factors, including small sample sizes for both the sphynx and control cats. Owing to the small sample size, factors that can impact follicle activity and density, such as photoperiod and age, were not accounted for in our analysis. However, all sphynx cats had anagen-dominant hair cycles (including a 10-year-old cat that had 80% anagen follicles) and all control cats had telogen-dominant cycles. Furthermore, the mean age of both dermatoscopy groups (sphynx and control cats) was very similar. Most cats were sampled only from the thorax; though the few biopsies taken from other sites were similar histologically,more samples from other sites may have revealed differences.

本研究受到许多因素的限制，包括斯芬克斯猫和对照猫的样本量均较小。由于样本量较小，我们的分析中未考虑可影响毛囊活性和密度的因素，如光照周期和年龄。然而，所有的斯芬克斯猫都有生长期为主的毛发周期（包括一只10岁的猫，有80%的生长期毛囊），所有的对照猫都有生长期为主周期。此外，两个皮肤镜组（斯芬克斯猫和对照猫）的平均年龄非常相似。大多数猫仅从胸部采样；尽管从其他部位采集的少数活检组织在组织学上相似，但其他部位的更多样本可能显示差异。

 

Immunohistochemical studies identified an abnormal distribution of keratin 71 in mouse KRT71 mutants, and scanning electron microscopy was also used to view hair shafts of Rex rodents and RCO12 and RCO13 mice. These techniques would be useful to confirm abnormal KRT71 expression, better describe follicular changes and better characterize the hair shafts of sphynx cats, but were beyond the scope of our study. Immunohistochemical techniques to identify the location of the keratin 71 protein in both normal cats and sphynx cats could elucidate potential differences in KRT71 expression between the sphynx cat and other species/breeds and reveal why coat and hair shaft changes are more severe in sphynx cats. Furthermore, follicular changes varied amongst sphynx cat follicles, with some appearing almost normal and others having severe abnormalities; immunohistochemical staining could identify differences in keratin 71 distribution between mildly and severely affected follicles.

免疫组织化学研究确定了角蛋白71在小鼠KRT71突变体中的异常分布，扫描电子显微镜也被用来观察Rex啮齿类动物和RCO12和RCO13小鼠的毛干。这些技术将有助于证实KRT71的异常表达，更好地描述毛囊变化和更好地表征斯芬克斯猫的毛干，但超出了我们的研究范围。免疫组织化学技术鉴定角蛋白71蛋白在正常猫和斯芬克斯猫中的位置可以阐明斯芬克斯猫和其他物种/品种之间KRT71表达的潜在差异，并揭示为什么斯芬克斯猫的被毛和毛干变化更严重。此外，斯芬克斯猫毛囊中的毛囊变化各不相同，一些几乎正常，其他有严重异常；免疫组织化学染色可以确定轻度和重度患病毛囊之间角蛋白71分布的差异。

 

Significant histological changes in the IRS of sphynx cats suggest that the sphynx KRT71 mutation does lead to abnormal protein expression in the IRS. Trichohyalin granules of the IRS play a vital role in hair shaft keratinization, and it is possible that the eosinophilic foci of the sphynx cat IRS represent abnormal trichohyalin granules. There were also occasional prominent, variably clear to pale, basophilic vacuolar-like changes observed in Huxley’s layer, though the exact cellular location of the change (intracellular versus extracellular) and nature of the swelling cannot be determined based on routine haematoxylin and eosin staining and light microscopy. Electron microscopy would be required for further detailed characterization of IRS changes. Abnormal anagen bulb morphology, an anagen-dominant hair cycle and an increase in kenogen follicles were also noted in sphynx cats. It is unclear whether the KRT71 mutation is involved in these abnormalities. Hair cycling is primarily regulated by follicular dermal papillae, and the abnormal morphology of the dermal papillae in sphynx cats may impact hair follicle cycling.

斯芬克斯猫IRS的显著组织学变化表明，斯芬克斯猫KRT71突变确实导致IRS的蛋白表达异常。IRS的毛透明素颗粒在毛干角化中起着至关重要的作用，斯芬克斯猫IRS的嗜酸性灶可能代表了异常的毛透明素颗粒。在赫胥黎氏层中也偶尔观察到明显的、不同程度的透明至浅嗜碱性空泡样变化，但根据常规苏木精和伊红染色以及光学显微镜检查无法确定变化的准确细胞位置（细胞内与细胞外）和肿胀性质。需要电子显微镜对IRS变化进行进一步详细表征。在斯芬克斯猫中也观察到生长期毛球形态异常、生长期为主毛发周期和无毛休止期毛囊增加。目前尚不清楚KRT71突变是否参与了这些异常。毛发周期主要由毛囊真皮乳头调节，斯芬克斯猫真皮乳头的异常形态可能影响毛囊周期。

 

In summary, our findings suggest that sphynx cats suffer from follicular dysplasia and production of abnormal hair shafts, without a decrease in the quantity of follicles. Many abnormal hair shafts are produced that protrude from follicular ostia but do not reach normal length. The presented histological findings of the sphynx cat IRS are similar to those of murine KRT71 mutants, suggesting abnormal hair shaft keratinization and implying that keratin 71 plays a vital role in hair shaft formation in cats. Further studies are needed to understand KRT71 expression and function in cats better and to explain the anagen-dominant hair cycle of sphynx cats.

综上所述，我们的研究结果表明，斯芬克斯猫患有毛囊发育异常和毛干产生异常，而毛囊数量没有减少。许多异常毛干从毛囊口突出，但未达到正常长度。斯芬克斯猫IRS的组织学发现与鼠KRT71突变体相似，提示毛干角化异常，并暗示角蛋白71在猫毛干形成中起重要作用。需要进一步的研究来更好地了解KRT71在猫中的表达和功能，并解释斯芬克斯猫的生长期为主毛发周期。

 

 

Figure 1. Compound follicle group from the lateral thorax of a sphynx cat. Note the large central primary follicle (large arrow) and associated lateral primary (small arrows) and secondary follicles.Most of the follicles are in anagen. Haematoxylin and eosin staining,

horizontal sectioning.

图1：斯芬克斯猫侧胸的复合毛囊组。注意大的中央初级毛囊（大箭头）和相关的外侧初级（小箭头）和次级毛囊。毛囊多处于生长期。苏木精和伊红染色，水平切片。

 

Figure 2. Typical follicles from a sphynx cats demonstrating slight bends (arrows) and a subjective decrease in follicular size (compare with sweat gland, marked with an arrowhead). Haematoxylin and eosin staining.

图2：一只斯芬克斯猫的代表性毛囊表现出轻微弯曲（箭）和毛囊大小的主观减小（与汗腺相比，用箭头标记）。苏木精和伊红染色。

 

 

Figure 3. (a,b) Two severely abnormal sphynx cat follicles with multiple directional changes. (c) Severely curved sphynx cat follicle. Haematoxylin and eosin staining.

图3.(a，b)两个严重异常的斯芬克斯猫毛囊，具有多个方向变化。(c)严重弯曲的斯芬克斯猫毛囊。苏木精和伊红染色。

 

 

Figure 4. Anagen follicle from a domestic short hair cat with a normal coat (a) and a sphynx cat (b). Note the differences in the inner root sheath (asterisks); the sphynx inner root sheath (b) is of nonuniform diameter, lacks a well-defined outer (Henle’s) layer (arrows), and contains large irregularly shaped eosinophilic foci as well as multiple clear vacuolar-type changes within Huxley’s layer. Haematoxylin and eosin staining.

图4：毛发正常的家养短毛猫(a)和斯芬克斯猫(b)的生长期毛囊。注意内根鞘的差异（星号）；斯芬克斯猫内根鞘(b)的直径不均匀，缺乏明确的外层（亨勒层）（箭），并且含有大的不规则形状的嗜酸性病灶以及Huxley层内的多个明确的空泡型变化。苏木精和伊红染色。

 

Figure 5. Hair follicles from a domestic short hair cat with a normal coat (a) and a sphynx cat (b). Differences in the inner root sheath (asterisks) between the sphynx and normal cat similar to those in Figure 4 are demonstrated in cross-section. In addition to the clear vacuolar change, there are also irregular pale basophilic vacuolar-type changes prominent in the sphynx inner root sheath. Haematoxylin

and eosin staining, horizontal sectioning.

图5.家养短毛猫的毛囊，毛发正常(a)，斯芬克斯猫(b)。在横截面中显示了与图4相似的斯芬克斯猫和正常猫之间的内根鞘（星号）差异。除明显的空泡改变外，在斯芬克斯猫的内根鞘中也有突出的不规则的淡嗜碱性空泡型改变。苏木精和伊红染色，水平切片。

 

Figure 6. Anagen bulbs from a normal cat (a) and sphynx cats (b–d). Note the flame-shaped dermal papillae (marked with an asterisk) of the normal cat and the orderly columnar epithelial cells surrounding the dermal papillae. The flame shape of the dermal papillae (asterisk) and surrounding orderly epithelial cell arrangement are lost to varying degrees in the anagen bulbs of sphynx cats (b–d). Haematoxylin and eosin staining.

图6.正常猫(a)和斯芬克斯猫(b-d)的生长期毛球。注意正常猫的火焰状真皮乳头（用星号标记）和真皮乳头周围有序的柱状上皮细胞。斯芬克斯猫(b-d)生长期毛球中真皮乳头的火焰状（星号）和周围有序的上皮细胞排列不同程度地丧失。苏木精和伊红染色。

 

Figure 7. Dermatoscopic images (5 mm 9 5 mm) from lateral thorax of cats with normal coats (a,b) and sphynx cats (c–f). The coat density for both sphynx cats and cats with normal coats appears similar. Sphynx cat hairs appear fine, and some are curved or kinked (two kinked hairs are marked with white arrows). Brown adherent debris can be seen on the sphynx cat skin (marked with black arrows). Cats with normal coats (a,b) were shaved with a 0.25 mm clipper blade.

图7.正常皮毛的猫(a，b)和斯芬克斯猫(c–f)侧胸的皮肤镜图像(5 mm 95 mm)。斯芬克斯猫和具有正常皮毛的猫的毛发密度几乎相似。斯芬克斯猫毛外观细小，有的弯曲或蜷缩（两根蜷缩的毛用白色箭头标记）。在斯芬克斯猫皮肤上可见棕色粘附碎片（用黑色箭头标记）。用0.25 mm剃刀头对具有正常毛发(a、b)的猫进行剃毛。

 

 

 

 

 

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