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.