|Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
RCT is a new congenital cataract mouse associated with microphthalmia, which has been found in SJL/J strain as a spontaneous recessive mutant Small but clear histological change in epithelial cells of the lens was observed at 2 days after birth. The opacity of the lens could be observed visually at 3 to 3.5 months of the age. This cataract is regulated by two recessive genes, rct and mrct (a modifier of rct), on Chromosome (Chr.) 4 and 5, respectively. The rct gene is essential for the onset of the cataract (Maeda, YY. et. al., Mann. Genome, 2001). To clone the rct gene, we generated 2,161 individuals of F_2 progeny between RCT and MSM/Ms which is an inbred strain established from Japanese wild mouse Mus musculus molossinus, and carried out fine mapping for the rct locus. As the result, the locus was found to be present on a DNA fragment of approximately 1.09 Mbps. Then, we generated a congenic strain (N_<13>), in which the DNA fragment including rct locus was substituted with the corresponding DNA of MSM/Ms mice, and found that mice in the strain have normal lens. Next, we performed BAC-transgenic rescue using several BAC clones, some of which can be expected to include the rct locus. We obtained several lines of transgenic (Tg) mice and phenotype survey is now in progress.
A new additional modifier locus, mrct2, was found on Chr.1. To examine the interaction between the mrct2 and mrct1 on Chr 5, we are now generating several congenic strains. Our preliminary results showed that mrct1 and mrct2 were located to be on 3 cM and 15 cM DNA fragments on corresponding chromosomes, respectively, and that the mrct1 showed relatively stronger effect than the mrct2. Both modifiers also showed a synergetic effect.