Retrotransposon-Mediated Fgf5^go-Utr Mutant Mice with Long Pelage Hair

Abstract

We found 6 spontaneous mutant mice with long pelage hair in our ICR breeding colony. The abnormal trait was restricted to long hair in these mice, which we named moja. They were fertile and showed the same growth and behavior as wild-type mice. To investigate the manner of the genetic inheritance of the moja allele, offspring were bred by mating the moja mice; all offspring had long pelage hair. Furthermore, we performed a reciprocal cross between moja mice and wild-type ICR mice with normal hair. All offspring exhibited normal hair suggesting an autosomal recessive inheritance of the trait. The moja/moja hair phenotype was maintained in skin grafted onto nude mice, suggesting that circulating or diffusible humoral factors regulating the hair cycle are not involved in the abnormal trait. The phenotype of moja/moja mice is similar to that of Fgf5-deficient mice. Therefore, we examined the expression of Fgf5 by RT-PCR in moja/moja mice. As expected, no Fgf5 expression was found in moja/moja mouse skin. PCR and DNA sequence analyses were performed to investigate the structure of the Fgf5 gene. We found a deletion of a 9.3-kb region in the Fgf5 gene including exon 3 and its 5’ and 3’ flanking sequences. Interestingly, the genomic deletion site showed insertion of a 498-bp early transposon element long terminal repeat. Taken together, these results suggest that the long hair mutation of moja/moja mice is caused by disruption of Fgf5 mediated by insertion of a retrotransposon.