title: A spontaneous mutation in the desmoglein 4 gene underlies hypotrichosis in a new lanceolate hair rat model.
abstract: A recessive hairless mutation arose spontaneously in a congenic line of spontaneously hypertensive rats SHR.BN-(D1Mit3-Igf2)/Ipcv. The mutant rats develop generalized alopecia except for partial hair growth on their heads. Affected animals of the congenic line were crossed with LEW rats and randomly bred for several generations. A genome scan in 74 affected and 75 unaffected offspring localized the mutant gene on rat chromosome 18p12, near the marker D18Rat107, which is closely linked to the desmosomal cadherin gene cluster, syntenic to mouse chromosome 18 and human chromosome 18q12. Recently, the mouse and rat phenotypes lah/lah (lanceolate hair) and lah(J)/lah(J)(lanceolate hair-J) were found to be caused by mutations in the desmoglein 4 (Dsg4) gene. Direct sequencing of the Dsg4 gene in the SHR revealed a homozygous C-to-T transition generating a premature termination codon within exon 8 in the affected animals. Further studies on the skin histology in affected rats demonstrated features consistent with a lanceolate hair mutation, providing further support for the crucial role of desmoglein 4 in hair shaft differentiation.
authors.affiliation: Gene Mapping Center, Max Delbruck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Meyer
authors.forename: Hisham
authors.initials: H
authors.lastname: Bazzi
authors.forename: Vaclav
authors.initials: V
authors.lastname: Zidek
authors.forename: Alena
authors.initials: A
authors.lastname: Musilova
authors.forename: Michal
authors.initials: M
authors.lastname: Pravenec
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Kurtz
authors.forename: Peter
authors.initials: P
authors.lastname: Nurnberg
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D015820:Cadherins / Q000235:genetics*; D002874:Chromosome Mapping; D002875:Chromosomes; D018389:Codon, Nonsense; D018388:Codon, Terminator; D051182:Desmogleins; D005091:Exons; D008040:Genetic Linkage; D006197:Hair / Q000002:abnormalities* / Q000473:pathology; D006720:Homozygote; D007039:Hypotrichosis / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D051381:Rats; D011917:Rats, Inbred Lew; D011918:Rats, Inbred SHR; D011922:Rats, Mutant Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D026801:Synteny
chemical_list: D015820:Cadherins; D018389:Codon, Nonsense; D018388:Codon, Terminator; D051182:Desmogleins; C492523:Dsg4 protein, rat