A nonsense nucleotide substitution in the oculocutaneous albinism II gene underlies the original pink-eyed dilution allele (Oca2(p)) in mice.
The original pink-eyed dilution (p) on chromosome 7 is a very old spontaneous mutation in mice. The oculocutaneous albinism II (Oca2) gene has previously been identified as the p gene. Oca2 transcripts have been shown to be absent in the skin of SJL/J mice with the original p mutant allele (Oca2(p)); however, the molecular genetic lesion underlying the original Oca2(p) allele has never been reported. The NCT mouse (commonly known as Nakano cataract mouse) has a pink-eyed dilution phenotype, which prompted us to undertake a molecular genetic analysis of the Oca2 gene of this strain. Our genetic linkage analysis suggests that the locus for the pink-eyed dilution phenotype of NCT is tightly linked to the Oca2 locus. PCR cloning and nucleotide sequence analysis indicates that the NCT mouse has a nonsense nucleotide substitution at exon 7 of the Oca2 gene. Examination of three mouse strains (NZW/NSlc, SJL/J, and 129X1/SvJJmsSlc) with the original Oca2(p) allele revealed the presence of a nonsense nucleotide substitution identical to that in the NCT strain. RT-PCR analysis revealed that the Oca2 transcripts were absent in the skin of NCT mice, suggesting intervention of the nonsense-mediated mRNA decay pathway. Collectively, the data in this study indicate that the nonsense nucleotide substitution in the Oca2 gene underlies the Oca2(p) allele. Our data also indicate that the NCT mouse can be used not only as a cataract model, but also as a model for human type II oculocutaneous albinism.
Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Haruka
H
Shoji
Yukiko
Y
Kiniwa
Ryuhei
R
Okuyama
Mu
M
Yang
Keiichi
K
Higuchi
Masayuki
M
Mori
D016115:Albinism, Oculocutaneous / Q000235:genetics*; D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002386:Cataract; D018389:Codon, Nonsense / Q000235:genetics*; D004195:Disease Models, Animal; D057915:Drug Substitution; D005091:Exons / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D059365:Nonsense Mediated mRNA Decay / Q000235:genetics*; D009711:Nucleotides / Q000235:genetics*; D010641:Phenotype
D002352:Carrier Proteins; D018389:Codon, Nonsense; D008565:Membrane Proteins; D009711:Nucleotides; C076239:P protein, mouse