International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

A16. Genetic Analysis of Autosomal Recessive Cataract Gene, lr2, using Intersubspecific F2 mice: Fine Mapping and Exclusion of Several Candidate Genes

Sang Dal Rhee1, Sungjoo Kim Yoon2, Yeong-Gwan Park3, Hyoungnam Lee2, Sung-Don Yang1, Masaaki Okumoto3, Kozaburo Esaki1, Chang-Woo Song1, and Sang-Seop Han1
1Toxicological Research Center, KRICT, Taejon Korea
2Research Institute of Molecular Genetics, Catholic Medical School, Seoul, Korea
3RIAST, Osaka Prefecture University, Osaka, Japan

We previously localized lens rupture 2 gene (lr2) causing cataract to mouse chromosome 14. To refine the position of lr2 gene prior to positional cloning, we have generated intersubspecific F2 mice between cataract mutant mice, CXSD and Mus musculus molossinus (MSM/Ms or MSM). Using total of 586 progeny, of which 444 mice were normal and 142 were cataractous, we determined the order of microsatellite markers and several candidate genes using combination of restriction fragment length polymorphism(RFLP), simple sequence length polymorphisms (SSLPs) and single strand conformational polymorphisms(SSCPs) analysis. The order from centromere to telomere was followings: D14Mit156- D14Mit88 - D14Mit235 - (D14Mit102, 203, Clu, Raftk) - (D14Mit143, 158, 262) - (D14Mit28, 6.1) - (D14Mit87) - (D14Mit86, 217, 216) - (D14Mit39, 159, Adam7) - (D14Mit89, 237) - D14Mit67 - D14Mit34. Additionally, Blk, Ctsb, and Gja3 were located proximal side of D14Mit88. Homozygosity mapping of 142 F2 cataractous mice and additive mating experiment revealed the commonly-inherited regions at D14Mit28 and D14Mit87, which contains the region syntenic to human Chr 8p21-22. We concluded that lr2 locus was placed in the region between (D14Mit143, 158, 262) and (D14Mit86, 217, 216), approximately 0.6 cM interval, thus excluding Blk, Ctsb, Gja3, Clu, Raftk, and Adam7 as candidate genes for lr2 gene.

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