title: Mutation in Mpzl3, a novel [corrected] gene encoding a predicted [corrected] adhesion protein, in the rough coat (rc) mice with severe skin and hair abnormalities.
abstract: The rough coat (rc), an autosomal-recessive mutation, arose spontaneously in C57BL/6J mice. Homozygous rc mice develop severe skin and hair abnormalities, including cyclic and progressive hair loss and sebaceous gland hypertrophy. The rc locus was previously mapped to Chromosome 9. To elucidate the genetic basis underlying the rc phenotype development, we carried out positional cloning, and mapped the rc locus to a 246-kb interval. We identified a missense mutation within a novel open reading frame in the rc/rc mice, which is predicted to encode a cell adhesion molecule with the highest homology to myelin protein zero (MPZ) and myelin protein zero-like 2 (MPZL2, also called epithelial V-like antigen). We therefore named this gene Mpzl3 (myelin protein zero-like 3). The mutation in the rc/rc mice occurred at a highly conserved residue within the conserved Ig-like V-type domain, thus likely altering the MPZL3 protein function. Reverse transcriptase-PCR and Western blot analyses revealed expression of the Mpzl3 gene in various adult organs, including the skin. Using indirect immunofluorescence, we detected MPZL3 protein in the keratinocytes and sebocytes in the skin. Results from this study identified a novel gene encoding a predicted adhesion protein whose mutation in the rc/rc mice likely caused the rc phenotype.
authors.affiliation: The Cardiovascular Research Center, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA. tongyu@pbrc.hawaii.edu
authors.forename: Tongyu
authors.initials: T
authors.lastname: Cao
authors.forename: Peter
authors.initials: P
authors.lastname: Racz
authors.forename: Kornelia M
authors.initials: KM
authors.lastname: Szauter
authors.forename: Gergely
authors.initials: G
authors.lastname: Groma
authors.forename: Garrett Y
authors.initials: GY
authors.lastname: Nakamatsu
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fogelgren
authors.forename: Eszter
authors.initials: E
authors.lastname: Pankotai
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: He
authors.forename: Katalin
authors.initials: K
authors.lastname: Csiszar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008040:Genetic Linkage; D006201:Hair Diseases / Q000235:genetics* / Q000473:pathology; D006984:Hypertrophy; D015603:Keratinocytes / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D010641:Phenotype; D012627:Sebaceous Glands / Q000502:physiology; D012720:Severity of Illness Index; D012871:Skin Diseases / Q000235:genetics* / Q000473:pathology
chemical_list: D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; C520409:Mpzl3 protein, mouse