RRC ID 21789
Author Mori M, Gotoh S, Taketani S, Hiai H, Higuchi K.
Title Hereditary cataract of the Nakano mouse: Involvement of a hypomorphic mutation in the coproporphyrinogen oxidase gene.
Journal Exp Eye Res
Abstract The Nakano cataract (NCT) is a recessive disorder in the mouse linked to the nct locus on chromosome 16. In this study, we positionally cloned the critical gene in the nct locus. Herein, we report that cataracts in the BALB/c-nct/nct mouse are caused by a hypomorphic mutation in the coproporphyrin oxidase gene (Cpox), encoding the enzyme responsible for catalyzing oxidative decarboxylation of the heme precursor, coproporphyrinogen III, in the heme biosynthetic pathway. BALB/c-nct/nct mice are homozygous for a G to T nucleotide substitution in the Cpox gene, which results in a p.R380L amino acid substitution in the CPOX protein. The CPOX isoform with the p.R380L substitution retained only 15% of the activity of the wild type isoform. BALB/c-nct/nct mice had excessive accumulation of coproporphyrin III in the lens. The NCT phenotype was normalized by the introduction of a wild type Cpox transgene. The mechanisms by which impairment of CPOX leads to lens opacity in the NCT are elusive. However, our data illuminate a hitherto unanticipated involvement of the heme biosynthesis pathway in lens physiology.
Volume 112
Pages 45-50
Published 2013-7-1
DOI 10.1016/j.exer.2013.04.005
PII S0014-4835(13)00093-6
PMID 23631845
MeSH Amino Acid Substitution Animals Cataract / genetics* Cataract / metabolism Coproporphyrinogen Oxidase / genetics* Coproporphyrinogen Oxidase / metabolism Coproporphyrins / metabolism Disease Models, Animal* Eye Diseases, Hereditary / genetics* Eye Diseases, Hereditary / metabolism Female Heme / metabolism Homozygote Male Mice Mice, Inbred BALB C Mice, Mutant Strains Mice, Transgenic Mutation, Missense* Phenotype Polymerase Chain Reaction RNA, Messenger / genetics
IF 3.011
Times Cited 6
Mice RBRC00422