129S1.B6-Pex10^m1Nisw/J

Stock number: 027330
Product name: Pex10^CY
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

Pex10^CY mice carry an ENU-generated point mutation of the Pex10 gene, exhibit abnormal neurodevelopment, and may be useful in studies of peroxisomal biogenesis disorders.

Detailed description

Mutations in the human PEX10 gene cause Zellweger spectrum of Peroxisome Biogenesis Disorder types 6A and 6B. These chemically-induced (ENU) mutant mice carry a single G to A base pair change in the Pex10 gene, resulting in a C294Y amino acid change that disrupts the second zinc RING finger binding domain. Most (98%) homozygotes die within hours of birth. Homozygous embryos begin to exhibit reduced locomotion at E17.5, and at birth are cyanoic and have no milk in their stomachs. Surviving homozygotes are significantly smaller in size than wildtype controls and display an ataxic gait. Very long chain fatty acids (VLCFA) levels are approximately 10-fold higher, and plasmalogen levels are approximately 21-fold lower in E18.5 homozygous embryos. Defective axon bundling by Schwann cells and axonal defects are observed in the sciatic nerves of homozygous embryos. Defects in neuromuscular synapses are found in soleus muscles, while deficits in axon extension, abnormal Schwann cell location and fewer Schwann cells in diaphragm muscles are also noted. Fibroblasts from homozygous embryos exhibit diffuse immunolabeling of the peroxisomal marker, catalase, compared to the punctate immunolabeling pattern observed in fibroblasts from wildtype control mice. During backcrossing, the Y chromosome may not have been fixed to the 129S1/SvImJ genetic background.

Development

Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder C57BL/6J mice, a forward genetic screen was utilized to identify mice exhibiting embryonic locomotor defects. The founder Pex10^CY male was crossed to 129S1/SvImJ wildtype female mice. Sequencing of multiple loci revealed a single base pair change G to A, resulting in the C294Y amino acid change, which disrupts the second zinc RING finger binding domain encoded by Pex10. The mice were then backcrossed to 129S1/SvImJ for 12 generations. During backcrossing, the Y chromosome may not have been fixed to the 129S1/SvImJ genetic background. Upon arrival at The Jackson Laboratory, the mice were crossed to 129S1/SvImJ (Stock No. 002448) at least once to establish the colony.

Allele

Symbol: Pex10^m1Nisw
Name: mutation 1, Lee Niswander
MGI accession ID: MGI:5638060
Generation method: Chemically induced (ENU)
Marker symbol: Pex10
Marker name: peroxisomal biogenesis factor 10
Chromosome: 4
Strain of origin: C57BL/6J
Molecular note: ENU induced a single base pair change from G to A, that results in the amino acid substitution of a cysteine for tyrosine at position 294 (C294Y), which disrupts the second zinc RING finger binding domain.