B6J(129S7)-Wrd81^nur5/PopJ

Stock number: 029024
Product name: Nur5
Research areas: Neurobiology Research, Research Tools

Description

ENU-induced Nur5 mice exhibit Purkinje and photoreceptor cell loss. They may be useful in studying Purkinje and photoreceptor cell survival.

Detailed description

Nur5 mice contain an ENU-induced T to C transition of nucleotide 4046 in exon 4 of the Wdr81 (WD repeat domain 81) gene. Wrd81 is expressed in the brain and is involved in the maintenance of normal mitochondrial structure and organization. It also promotes Purkinje and photoreceptor cell survival. Mutations of Wdr81 have been associated with a disease locus in a consanguineous Turkish family that suffers from cerebellar ataxia, mental retardation, and quadrupedal locomotion syndrome (CAMRQ2: Cerebellar Ataxia, Mental Retardation, and Dysequilibrium Syndrome 2). Nur5 mice exhibit Purkinje cells loss starting at P28 leading to cerebellar ataxia and cerebellar atrophy. They also display severe progressive photoreceptor cell loss starting around P15. Homozygotes develop a quivering gait at approximately P60. Heterozygous mice are viable and fertile. The donating investigator has not attempted to breed homozygous mice together.

Development

Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder C57BL/6J-In(11Trp53;11Wnt3)8Brd mice, a forward genetic screen was utilized to identify a family of Nur5 mice displaying tremors, abnormal gait, Purkinje cell degeneration, and photoreceptor cell loss. Using polymorphic marker mapping, a missense mutation was identified in the Wdr81 (WD repeat domain 81) gene. Sequencing identified an T to C transition of nucleotide 4046 in exon 4 of Wdr81. These Nur5 mice were bred to littermates or to C57BL/6J mice to maintain a colony. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664). The In(11Trp53;11Wnt3)8Brd inversion was not maintained in the colony.

Allele

Symbol: Wdr81^nur5
Name: neurological 5
MGI accession ID: MGI:2671731
Generation method: Chemically induced (ENU)
Synonyms: nur^m05Jus; shaky 5
Marker symbol: Wdr81
Marker name: WD repeat domain 81
Marker synonyms: CAMRQ2; CHMRQ; HYC3; MGC:32441; MGC32441; nur5; PPP1R166; RGD1311334; shakey 5; SORF-2
Chromosome: 11
Strain of origin: C57BL/6J
Molecular note: This phenotypic mutant was identified in an ENU mutagenesis screen at the Baylor College of Medicine. Sequencing identified a T to C transition of nucleotide 4046 in exon 4 of Wdr81. This missense mutation results in an amino acid substitution (L1349P) in the major facilitator superfamily (MFS) domain of the protein. Expression of WDR81 protein in the cerebellum and retina is comparable to wild-type.