title: Mouse paracentric inversion In(3)55Rk mutates the urate oxidase gene.
abstract: The paracentric inversion In(3)55Rk on mouse Chromosome 3 (Chr 3) was induced by cesium irradiation. Genetic crosses indicate the proximal breakpoint cosegregates with D3Mit324 and D3Mit92; the distal breakpoint cosegregates with D3Mit127, D3Mit160, and D3Mit200. Giemsa-banded chromosomes show the inversion spans approximately 80% of Chr 3. The proximal breakpoint occurs within band 3A2, not 3B as reported previously; the distal breakpoint occurs within band 3H3. Mice homozygous for the inversion exhibit nephropathy indicative of uricase deficiency. Southern blot analyses of urate oxidase, Uox, show two RFLPs of genomic mutant DNA: an EcoRI site between exons 4-8 and a BamHI 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 heterozygotes, using a cosmid clone containing genomic wild-type DNA for Uox exons 2-4, shows that a 5' segment of the mutated Uox allele on the inverted chromosome has been transposed from the distal breakpoint region to the proximal breakpoint region. Clinical, histopathological, and Northern analyses indicate that our radiation-induced mutation, uox(In), is a putative null.
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA. sac@jax.org
authors.forename: S A
authors.initials: SA
authors.lastname: Cook
authors.forename: E C
authors.initials: EC
authors.lastname: Akeson
authors.forename: C
authors.initials: C
authors.lastname: Calvano
authors.forename: K R
authors.initials: KR
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Mandell
authors.forename: N L
authors.initials: NL
authors.lastname: Hawes
authors.forename: R T
authors.initials: RT
authors.lastname: Bronson
authors.forename: T H
authors.initials: TH
authors.lastname: Roderick
authors.forename: M T
authors.initials: MT
authors.lastname: Davisson
mesh_terms: D000483:Alleles; D000818:Animals; D015139:Blotting, Southern; D002871:Chromosome Banding; D007446:Chromosome Inversion; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D007674:Kidney Diseases / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014503:Urate Oxidase / Q000235:genetics*; D014527:Uric Acid / Q000097:blood / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D014527:Uric Acid; D014503:Urate Oxidase