title: The lanceolate hair rat phenotype results from a missense mutation in a calcium coordinating site of the desmoglein 4 gene.
abstract: Desmosomal cadherins are essential cell adhesion molecules present throughout the epidermis and other organs, whose major function is to provide mechanical integrity and stability to epithelial cells in a wide variety of tissues. We recently identified a novel desmoglein family member, Desmoglein 4 (Dsg4), using a positional cloning approach in two families with localized autosomal recessive hypotrichosis (LAH) and in the lanceolate hair (lah) mouse. In this study, we report cloning and identification of the rat Dsg4 gene, in which we discovered a missense mutation in a naturally occurring lanceolate hair (lah) rat mutant. Phenotypic analysis of lah/lah mutant rats revealed a striking hair shaft defect with the appearance of a lance head within defective hair shafts. The mutation disrupts a critical calcium binding site bridging the second and third extracellular domains of Dsg4, likely disrupting extracellular interactions of the protein.
authors.affiliation: School of Biomedical and Biological Sciences, University of Durham, Durham, United Kingdom.
authors.forename: Colin A B
authors.initials: CA
authors.lastname: Jahoda
authors.forename: Ana
authors.initials: A
authors.lastname: Kljuic
authors.forename: Ryan
authors.initials: R
authors.lastname: O'Shaughnessy
authors.forename: Neil
authors.initials: N
authors.lastname: Crossley
authors.forename: C Jenna
authors.initials: CJ
authors.lastname: Whitehouse
authors.forename: Mark
authors.initials: M
authors.lastname: Robinson
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Reynolds
authors.forename: Michel
authors.initials: M
authors.lastname: Demarchez
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Porter
authors.forename: Lawrence
authors.initials: L
authors.lastname: Shapiro
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D051182:Desmogleins; D003896:Desmosomes / Q000737:chemistry; D023281:Genomics; D006197:Hair / Q000002:abnormalities*; D007039:Hypotrichosis / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D051381:Rats; D011922:Rats, Mutant Strains; D012867:Skin / Q000473:pathology
chemical_list: D015820:Cadherins; D018076:DNA, Complementary; D051182:Desmogleins; C492523:Dsg4 protein, rat; D002118:Calcium