The Lanceolate Hair Rat Phenotype Results from a Missense Mutation in a Calcium Coordinating Site of the Desmoglein 4 Gene

The study identified a missense mutation in the Desmoglein 4 (Dsg4) gene in a naturally occurring lanceolate hair (lah) rat mutant, which resulted in a distinctive hair shaft defect resembling a lance head. This mutation disrupted a critical calcium binding site in Dsg4, likely affecting extracellular interactions of the protein. The lah/lah rats exhibited phenotypic similarities to the lanceolate hair mouse and human localized autosomal recessive hypotrichosis (LAH), making this rat model valuable for studying inherited hypotrichosis in humans. The mutation also caused increased cell proliferation and upregulation of hyperproliferation markers in the epidermis.