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Alopecia X in a cloned Pomeranian dog
一只克隆博美犬的X型脱毛
作者：Sébastien Deleporte | Pascal Prelaud | Catherine Laffort
翻译：王帆
Abstract
A two-year-old Pomeranian dog with Alopecia X was cloned after accidental death. Despite earlier castration, the cloned animal developed the same lesions of Alopecia X at the same age. This observation suggests that the disease is due to genetically programmed hair cycle arrest without strong environmental influences.
摘要
一只2岁X脱毛博美患犬在意外死亡后被克隆。尽管早期进行了去势手术，但克隆动物在同一年龄出现了相同的X脱毛病变。这一观察结果表明，这种疾病是由于遗传程序性的毛发周期停滞，而没有强烈的环境影响。
INTRODUCTION
介绍
Alopecia X (hair cycle arrest) is a frequent cause of noninflammatory alopecia in Pomeranians and other ‘plushcoated’ dogs. The typical clinical form is progressive, noninflammatory and symmetrical alopecia of the neck, trunk, tail, perineum, and caudal thighs, which is initially nonpruritic. The differential diagnosis includes other noninflammatory alopecias, such as postclipping alopecia, follicular dysplasia and endocrinopathies, and inflammatory dermatoses such as demodicosis and sebaceous adenitis. Miscellaneous treatments which are proposed to temporarily reactivate hair growth include gonadectomy or chemical castration (especially in the intact male dog), anti-androgens, melatonin, growth hormone, interference with adrenocortical synthesis of steroidal hormones (through use of oral drugs such as trilostane or mitotane) and physically induced trauma, as may be produced by microneedling or lowlevel laser. The pathomechanism of this disease is still obscure and a genetic basis has been thought to be highly plausible, which codes for an as-yet unidentified hormonal imbalance or a defect residing at the level of the hair follicle.
脱毛X(毛发周期停滞)是博美犬和其他长绒毛犬非炎性脱毛的常见原因。典型的临床表现为颈部、躯干、尾部、会阴和大腿尾端的进行性、非炎性和对称性脱毛，最初无瘙痒。鉴别诊断包括其他非炎性脱毛，如剃毛后脱毛、毛囊发育不良和内分泌疾病，以及炎性皮肤病，如蠕形螨病和皮脂腺炎。用于暂时恢复毛发生长的其他治疗包括性腺切除术或化学去势术(尤其未去势雄性犬)、抗雄激素、褪黑素、生长激素、干扰肾上腺皮质类固醇激素的合成(通过使用口服药物，如曲洛斯坦或米托坦)和物理诱导的创伤，如微针或低强度激光产生的创伤。这种疾病的病理机制仍不清楚，高度相信具有遗传基础，它编码了一种尚未确定的激素失衡或位于毛囊水平的缺陷。
CASE REPORT
病例报告
A two-year-old male Pomeranian dog living in south-west France (Bordeaux) was presented in January 2014 with a typical form of Alopecia X. This disease had been progressive over the previous year, with alopecia affecting well-demarcated areas of the trunk, neck and forelimbs, and sparing the face and feet. Mild generalised cutaneous xerosis and hyperpigmentation were present (Figure 1a), and hair regrowth was noted at previous biopsy sites. Routine endocrine tests were within normal limits. Multiple skin biopsies were collected from haired and nonhaired areas. Histopathological examination revealed a predominance of kenogen follicles (hairless telogen) with excessive trichilemmal keratinisation expanding the outer root sheaths, creating ‘flame follicles’ and moderateto-severe follicular hyperkeratosis. Moderate multifocal hyperpigmentation was present in all layers of the epidermis, and there was mild hair follicle dysplasia. No signs of inflammation were detected in any sections. These findings combined with the clinical appearance and history confirmed Alopecia X.
2014年1月，一只生活在法国西南部(波尔多)的两岁雄性博美犬出现了典型的X脱毛。这种疾病在过去一年中一直在进展，脱毛影响躯干、颈部和前肢的边界清楚的区域，而面部和足部不受影响。患犬有轻度全面性皮肤干燥和色素沉着(图1a)，并且在之前的活检部位观察到毛发再生。常规内分泌检查均在正常范围内。从有毛和无毛区域采集多个皮肤活检。组织病理学检查显示，kenogen毛囊(无毛静止期)占主导地位，毛膜过度角化延伸至外根鞘，形成“火焰毛囊”和中-重度毛囊角化过度。表皮各层中度多灶性色素沉着，轻度毛囊发育不良。所有切片均未发现炎症症状。这些发现结合临床表现和病史确诊为X脱毛。
The dog was neutered in April 2014 and hair regrowth was partially observed on the trunk, followed by a relapse twomonths later. The dog died in September 2014 of unrelated causes, and his owner immediately arranged for the dog to be cloned in by a South Korean company (Sooam Biotech). A viable clone was born in August 2015, and like its predecessor, first developed clinical signs of Alopecia X at oneyear of age (Figure 1b). He was immediately neutered (threemonths earlier than the initial dog). Partial hair regrowth was noted, followed by relapse and worsening of the lesions threemonths later. The owners declined treatments other than daily use of a moisturising spray (Ermidra spray; ICF).
2014年4月，这只犬进行去势手术，在躯干上观察到部分毛发再生，两个月后复发。2014年9月，这只犬死于其他原因，它的主人立即安排韩国一家公司将这只犬克隆入体内。2015年8月诞生了一个存活的克隆犬，与原始犬一样，该克隆犬在1岁时首次出现X脱毛的临床症状(图1b)。该犬立即进行了去势手术(比原始犬早三个月)。部分毛发再生，3个月后病变复发、加重。除了每天使用保湿喷雾以外，主人没有进行其他治疗管理。
DISCUSSION
讨论
The observations of clinical outcomes in these two dogs supports the strong likelihood of a genetic component in the development of Alopecia X in Pomeranians. Both dogs developed alopecia at the same age regardless of their living conditions. The cloned dog had lived in a South Korean kennel for the first sevenmonths of its life, before being delivered to the owner who then resided in a dense urban environment. The progenitor dog had been adopted at twomonths of age and was raised in a semi-urban environment. For both dogs, castration produced only temporary hair regrowth with similar outcomes, even though the cloned dog was neutered earlier in the course of his disease.
对这两只犬的临床结果的观察，支持博美犬X脱毛的发生很可能与遗传因素有关。无论生活条件如何，这两只犬都在相同的年龄发生脱毛。这只克隆犬在出生后的前七个月一直生活在韩国的一个犬舍里，然后被送到主人那里，主人住在一个人口稠密的城市环境中。原始犬在两个月大时被收养，并在半城市环境中饲养。对于这两只犬来说，去势只产生了短暂的毛发再生，并且结果相似，但这只克隆犬在疾病的早期就进行去势手术了。
Numerous genes which code for enzymes involved in sex hormone metabolism are suspected to be up-or down regulated in Alopecia X cases. Therefore, it is difficult to imagine that a simple genetic test could be developed to identify at-risk animals. Alopecia X in the Pomeranian breed is anecdotally reported to be common in many countries, so high penetrance of risk genes throughout the breed may be expected. To reduce the incidence of new cases, affected dogs and their relatives should be removed from the breeding pool. These cases also illustrate the fact that dogs with genetically mediated diseases should not be cloned. Other considerations relevant to the practice of cloning dogs have been reviewed elsewhere.
在X脱毛病例中，疑似许多参与性激素代谢的基因编码酶的上调或下调导致发病。因此，很难想象能够开发出一种简单的基因测试来识别有风险的动物。据报道，博美犬X脱毛在许多国家都很常见，因此可以预期该犬种的风险基因具有较高的外显率。为减少新病例的发生，应避免患病犬及其亲属进行繁殖。这些案例也说明了一个事实，即患有遗传介导疾病的犬不应该被克隆。其他与克隆犬实践相关的考虑已经在其他地方进行了审查。
FIGURE 1 Skin lesions of a progenitor dog at twoyears of age (a) and its clone (b), each showing extensive symmetrical alopecia of the trunk, with hyperpigmentation.
图1两岁时原始犬(a)及其克隆犬(b)的皮肤病变，均表现为躯干大面积对称的脱毛，伴有色素沉着。
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发表于 2024-1-13 14:34:21
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