Mapping of Nakano Cataract Genencton Mouse Chromosome 16

Hayashi, Hiroshi; Kato, Satoko; Horiuchi, Yuka; Shimada, Reiji; Tsuruyama, Tatsuaki; Watanabe, Tomomasa; Matsubara, Akio

doi:10.1006/geno.1998.5286

Cited by 7 publications

(6 citation statements)

References 4 publications

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“…Another form of cataracts, which is formed postnatally without observed developmental alterations, is the Nakano cataract (nct; Takehana, 1990;Wada et al, 1991). The mutation was mapped to chromosome 16 (Hiai et al, 1998).…”

Section: Mutants Waiting For Molecular Characterizationmentioning

confidence: 99%

Congenital hereditary cataracts

Graw¹

2004

Int. J. Dev. Biol.

126

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Congenital cataracts are rare and occur in developed countries with a frequency of 30 cases among 100,000 births with a further 10 cases being diagnosed during childhood. They reflect mainly genetically caused developmental alterations in the lens and surrounding ocular tissues. Even if modern Human Genetics has made large steps forward in the characterization of human hereditary disorders, the underlying developmental processes can only be investigated in model organisms. The mouse is such a good model because of its similarity (as a mammal) and its genetic characterization. This review brings together our genetic and developmental knowledge of congenital, human cataracts with the corresponding mouse models. First, early events will be influenced by genes coding for transcription factors like Pax6, Pitx3, Maf or Sox. If the lens is maturing, mutations affecting the lens membranes (aquaporins/Mip, Lim-2 or connexins) or the structural proteins of the cytosol of the lens fiber cells (the crystallins) become more important. From a genetic point of view it becomes obvious that cataract-causing mutations are not distributed randomly. The discovery of a broad variety of genes important for eye and lens development made much progress in the recent years. Nevertheless, there still remains a long list of mutations to be characterized and functionally investigated both in mouse and man indicating a broad genetic heterogeneity in that which clinicians simply refer to as a "cataract".

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Section: Mutants Waiting For Molecular Characterizationmentioning

confidence: 99%

Congenital hereditary cataracts

Graw¹

2004

Int. J. Dev. Biol.

126

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“…We previously performed chromosomal mapping of the nct locus by breeding BALB/c-nct/nct × (BALB/c-nct/nct × MSM/Ms) backcross mouse progeny, and demonstrated that the locus is located in a region between 2 microsatellite marker loci, D16Mit5 and D16Mit185, on chromosome 16 (Hiai et al, 1998;Narita et al, 2002 Dcbld2,St3gal6,Cpox,Gpr15,Cldn25,Gabrr3,Mina,Crybg3,and Ar16) are expressed in a broad range of tissues, including the eye.…”

Section: Balb/c-nct/nct Has a Missense Mutation In The Coproporphyrinmentioning

confidence: 99%

“…Elucidation of the nct gene would help establish the sequence of biochemical, cellular, developmental, and physiological events that lead from lens epithelial cell damage to Cpox mutation in the Nakano cataract mouse 4 cataract formation. In the present study, we attempted positional cloning of the nct gene based on the prior mapping results of the nct on chromosome 16 (Hiai et al, 1998;Narita et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Hereditary cataract of the Nakano mouse: Involvement of a hypomorphic mutation in the coproporphyrinogen oxidase gene

Mori¹,

Gotoh²,

Taketani³

et al. 2013

Experimental Eye Research

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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.

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“…Genomic DNA were extracted from the kidneys of each backcrossed mouse and used in linkage analysis with microsatellite markers obtained from Research Genetics (Huntsville, AL, U.S.A.), as described previously (Hiai et al, 1998). Extensive screening for polymorphic markers on the middle segment of chromosome 16 between BALB/c-nct/nct and MSM/ Ms was carried out.…”

Section: Gene Mappingmentioning

confidence: 99%

“…In a previous study, we mapped the NCT gene on a 38±43 cM region from the centromere of chromosome 16 (Hiai et al, 1998). From its map position, we excluded MIP26 as the candidate gene suggested by Tanaka et al (1980) and Takehana (1990), but it was not possible to determine more plausible alternatives from the map position alone.…”

Section: Introductionmentioning

confidence: 98%

Genetic Analysis of Nakano Cataract and Its Modifier Genes in Mice

Narita

Wang

Kita

et al. 2002

Experimental Eye Research

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The Nakano Cataract (NCT) is an autosomal, recessive, single gene mutation in mice leading to an osmotic cataract induced by an endogenous inhibitor of Na, K-ATPase. In this report, we further refined the map position of the mutant locus to a <0.7c M segment between D16Mit5 and D16Mit185 in 1,000 BALB/c-nct/nct x(BALB/c- nct/nctxMSM)F1 backcrossed mice with PCR-based microsatellite analysis. The NCT in the original Nakano mice developed at 3 weeks of age, rapidly formed a pin-head type dense opacity, whereas the cataract in the congenic BALB/c- nct/nct mice developed at 5-6 weeks of age or later, slowly formed a diffuse opacity. A major histological difference was the presence or absence of heavy condensation of the lens nucleus. These two types of cataract were segregated in the backcrossed mice. Linkage analysis of the two subtypes among the backcrossed mice revealed two recessive BALB/c-derived modifier genes on chromosome 3 and 10.

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Mapping of Nakano Cataract Genencton Mouse Chromosome 16

Cited by 7 publications

References 4 publications

Congenital hereditary cataracts

Congenital hereditary cataracts

Hereditary cataract of the Nakano mouse: Involvement of a hypomorphic mutation in the coproporphyrinogen oxidase gene

Genetic Analysis of Nakano Cataract and Its Modifier Genes in Mice

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