Abstract
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.
Highlights
Three breeds of domestic cats (Felis silvestris catus) are characterized by a non-syndromic congenital hypotrichosis
Since a similar syndrome, called the nude syndrome, has been deciphered in mice, rats and humans and because the proband kitten died in its first months of age from a presumable intestinal infection, we opted for a candidate gene approach targeting the forkhead box N1 (FOXN1) gene which loss-of-function mutations had been shown to produce the nude phenotype in rodents and humans [15,20]
We identified eight polymorphisms in the exonic sequence of FOXN1, among which a c.1030_1033delCTGT deletion predicted to be a deleterious mutation; the c.[1030_1033delCTGT] allele yields a truncated protein lacking the intact DNA binding and activation domains, both involved in FOXN1 function
Summary
Three breeds of domestic cats (Felis silvestris catus) are characterized by a non-syndromic congenital hypotrichosis. Sphynx cats are homozygous for an autosomal recessive hairless allele (hr or Canadian hairless) of the KRT71 (keratin 71) gene [1]. Cats from the two related Donskoy and Peterbald breeds carry a semi-dominant hairless mutation, the molecular aetiology of which remains unknown [2]. Congenital hypotrichosis has been regularly reported in other purebred and outbred cats since 1924 [3,4,5,6,7,8,9]. PLOS ONE | DOI:10.1371/journal.pone.0120668 March 17, 2015
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