A deletion in FOXN1 is associated with a syndrome characterized by congenital hypotrichosis and short life expectancy in Birman cats.
A deletion in FOXN1 is associated with a syndrome characterized by congenital hypotrichosis and short life expectancy in Birman cats.
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DOI：
10.1371/journal.pone.0120668
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tiret L
中科院分区：
文献类型：
--
作者：
Abitbol M;Bossé P;Thomas A;Tiret L
伯曼猫品种（Felis silvestris catus）描述了一种常染色体隐性遗传综合征，其特征是先天性少毛症和预期寿命短。我们假设 FOXN1（叉头盒 N1）功能丧失等位基因与人类、小鼠和大鼠的裸表型相关，可能是伯曼猫中观察到的综合征的原因。据我们所知，在非人类、非啮齿类哺乳动物物种中从未描述过 FOXN1 自发突变。我们在伯曼猫的 FOXN1 中发现了隐性 c.1030_1033delCTGT 缺失。当存在两个拷贝时，该 4-bp 缺失与该综合征相关。我们的法国基因型伯曼猫小组中健康携带者的百分比估计为 3.2%。该缺失导致蛋白质中第 547 位出现移码和过早终止密码子。在计算机模拟中，截短的 FOXN1 蛋白被预测缺乏激活结构域和叉头 DNA 结合结构域的关键部分，这两个部分都参与 FOXN1 与其靶标之间的相互作用，这是促进正常毛发和胸腺上皮发育的强制性步骤。我们的结果扩大了哺乳动物中隐性 FOXN1 功能丧失等位基因的范围。可以进行 DNA 测试；它将帮助主人避免有风险的交配，并应防止这种病态突变在家猫科动物中传播。
An autosomal recessive syndrome characterized by congenital hypotrichosis and short life expectancy has been described in the Birman cat breed (Felis silvestris catus). We hypothesized that a FOXN1 (forkhead box N1) loss-of-function allele, associated with the nude phenotype in humans, mice and rats, may account for the syndrome observed in Birman cats. To the best of our knowledge, spontaneous mutations in FOXN1 have never been described in non-human, non-rodent mammalian species. We identified a recessive c.1030_1033delCTGT deletion in FOXN1 in Birman cats. This 4-bp deletion was associated with the syndrome when present in two copies. Percentage of healthy carriers in our French panel of genotyped Birman cats was estimated to be 3.2%. The deletion led to a frameshift and a premature stop codon at position 547 in the protein. In silico, the truncated FOXN1 protein was predicted to lack the activation domain and critical parts of the forkhead DNA binding domain, both involved in the interaction between FOXN1 and its targets, a mandatory step to promote normal hair and thymic epithelial development. Our results enlarge the panel of recessive FOXN1 loss-of-function alleles described in mammals. A DNA test is available; it will help owners avoid matings at risk and should prevent the dissemination of this morbid mutation in domestic felines.
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