P2.24 The Iffa Credo Rat is a New Desmoglein 4 Mutant Model

Hisham Bazzi, Ana Kljuic, Andrey Panteleyev, and Angela M. Christiano

Departments of Dermatology and Genetics & Development, Columbia University, College of Physicians & Surgeons, New York, NY

Desmosomes are intercellular junctions abundant in epithelial tissues that are subjected to mechanical stress such as the epidermis of the skin and the oral epithelium. The extracellular interacting interfaces of desmosomes are part of the transmembrane proteins known as desmogleins. So far, four desmogleins have been described in humans and rats. Rat desmoglein 4 (rDsg4) have very recently been identified and mutations in rDsg4 lead to a hypotrichosis phenotype in lanceolate rats. In this report, we show that the Iffa Credo rat, which exhibits a hairless phenotype, is a new null mutant model for rDsg4. Iffa Credo rats have sparse body hair and irregular broken whiskers. Histologically, their skin is thickened and the hair follicles are grossly abnormal.  A hallmark of all rodent desmoglein 4 mutants is the presence of an amorphous keratinized lance-head in the hair shaft (HS) of the hair follicle which leads to the hair breakage and loss. Iffa Credo rats show similar lance-heads in the HS. Upon sequencing the rDsg4 gene in the Iffa Credo rat, we have identified a large intragenic deletion spanning exons 2 to 10. The deletion is out of frame in exon 11 and RT-PCR showed a significant decrease in rDsg4 message supporting the hypothesis that this is a null model. Further studies on this desmoglein 4 model will extend our understanding of the essential function for this protein in hair follicle integrity and cycling.