Positional Cloning Of A Novel Gene In Uncoverd Mouse And Functional Analysis In Mouse Hair Follicle Development

Alopecia is a common illness in humans and the incidence of this disease is from 20% to 24%. It has many phenotypes such as androgenetic alopecia, alopecia areata, congenital alopecia, telogen effluvium and so on. Alopecia can result from inherent and environmental causes, such as food, pressure and so on. However, we have a poor knowledge about the genes that cause alopecia in humans. As mammalian models, hairless and hair loss mutant mice play a key role in searching new gene and finding their function.The uncovered coat mutation appeared spontaneously in BALB/c background. It inherited an autosomal semidominant (homozygote with uncovered coat, heterozygote with sparse hair). Except uncovered coat, the homozygote was also accompanied by growth retard and puberty delay.In this research, we first mapped this mutation to 69.25cm on the chromosome 11 then scan the mouse genome and found a novel gene, we named it as: Uncv. NCBI EntrzeGene GeneID: 109602, MGD(Mouse Genome Database) MGI: 1261908.In situ hybridization showed its location in epidermal, subcutis and hair follicle. The UNCV protein was predicted to be a trans-membrane protein.We constructed Uncv transgenic mice. The mice were crossed with uncovered mice,in its F2 mice we observed that UNCV protein can partly restore phenotype. We else crossed uncover mice to an Egf transgenic mouse, those F1 mice both with Egf over expression and heterozygote in mutated Uncv shows heavily sparse hair. We suggested that Uncv was participated in the EGF/EGFR signal pathway in modulating the hair follicle development.Western blot showed in the skin of uncovered mice the phospho-level of EGFR was lower than its wild type partner. Immunohistochemistry showed EGFR,Erk,Rb,Caspase-3 were not at where they used to be. In vitro cell transfection followed by Protein Tyrosine Kinase assay showed low phospho-transfer rate in cells transfected by mutant Uncv construct. We also found that Uncv promotes cleavage of Epigen, a member of EGF/EGFR family.