Mouse paracentric inversion In(3)55Rk mutates the urate oxidase gene

The paracentric inversion In(3)55Rk on mouse Chromosome 3 (Chr 3) was induc ed by cesium irradiation. Genetic crosses indicate the proximal breakpoint cosegregates with D3Mit324and D3Mit92; the distal breakpoint cosegregates w ith D3Mit127. D3Mit160, and D3Mit200. Giemsa-banded chromosomes show the in version spans similar to 80% of Chr 3. The proximal breakpoint occurs withi n band 3A2, not 3B as reported previously; the distal breakpoint occurs wit hin band 3H3. Mice homozygous for the inversion exhibit nephropathy indicat ive of uricase deficiency. Southern blot analyses of urate oxidase, Uox, sh ow two RFLPs of genomic mutant DNA: an EcoRI site between exons 4-8 and a B amHI site 3' to exon 6. Mutant cDNA fails to amplify downstream of base 844 at the 3' end of exon 7. FISH analysis of chromosomes from inversion heter ozygotes, using a cosmid clone containing genomic wild-type DNA for Uox exo ns 2-4, shows that a 5' segment of the mutated Uox allele on the inverted c hromosome has been transposed from the distal breakpoint region to the prox imal breakpoint region. Clinical, histopathological, and Northern analyses indicate that our radiation-induced mutation, uox(ln), is a putative null. Copyright (C) 2001 S. Karger AG, Basel.