A new autosomal recessive mutation jcpk (juvenile congenital polycystic disease) was generated by chlorambucil mutagenesis. In the homozygous condition, this mutation causes a severe polycystic disease (PKD) which is more severe than previously described mouse PKD mutants. Homozygotes are detectable as early as 4 days and have grossly enlarged kidneys. Histologically, homozygote kidneys are highly abnormal even at birth, with cysts appearing throughout the kidney. Extreme dilatations of the bile ducts and pancreatic ducts are often seen. A late onset glomerulocystic disease is present in approximately 25% of the heterozygotes. The investigators have mapped the jcpk mutation to mouse chromosome 10. jcpk has recently been found to be allelic the bck mutation. By an extensive backcross, a fine genetic map of the region around the jcpk locus has been made. This map should enable the investigators to positionally clone the jcpk locus.
The Specific Aims of the proposal are to: (1) build a YAC and BAC contig of the region surrounding the jcpk locus; (2) identify candidate genes for this locus; (3) identify, clone, and characterize the jcpk gene; and (4) characterize the genetics of cystic disease in +/jcpk heterozygotes. Arrayed cDNA libraries will be used for some of these studies. In addition, genetic experiments involving DNA mismatch repair-deficient mice and transgenic mice will be conducted.
| Cogswell, Cathy; Price, Sarah J; Hou, Xiaoying et al. (2003) Positional cloning of jcpk/bpk locus of the mouse. Mamm Genome 14:242-9 |
| Guarnieri, Mary H; Cacheiro, Nestor L; Rudofsky, Ulrich H et al. (2002) A chromosomal translocation causing multiple abnormalities including open eyelids at birth and glomerulonephritis. Mamm Genome 13:416-22 |
| Manley, K; Shirley, T L; Flaherty, L et al. (1999) Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic mice. Nat Genet 23:471-3 |
