POSITIONAL CLONING OF HEREDITARY CATARACTS IN MICE

点击翻译按钮获取中文摘要

We performed positional cloning of the genes responsible for two mouse hereditary cataracts found in Japan. These genes are supposedly involved in organogenesis and maintenance of transparency of the lens. According to the results of fine mapping of Rupture of lens cataract (RLC), we sequenced a number of the cDNA clones at the map positions obtained from the mouse full-length cDNA encyclopedia developed by RIKEN. One of cDNA clones, rlcl, was found to have deletion of 27 bp, when compared with the normal cDNA sequence. This deletion was specific to RLC mutant. Rabbit antiserum to the C-terminus peptide of rlcl product detected a 110 kDa polypeptide in the lens. Immunohistochemistry with this antiseum revealed unique distribution in lens epithelium, nervous system and other tissues. Mechanism of cataractgenesis is now under investigation. On the other hand, the same positional approach in Nakano cataract (NCT) demonstrated a 13 bp deletion in nctl cDNA. This deletion was conserved in NK11, an established cell line of lens epithelium provided from NEL Careful examination of the lenses in N2 cross to MSM revealed two distinct forms of lens opacity in respect to distribution of cloudiness and latent period. We could map two modifier loci determining the subtypes of NCT cataract on Chr. 3 and 10.To further confirm that these deletions are indeed causative mutation, rescue with normal full size cDNA and targeting experiments are now in progress in this laboratory.