129S-Pnpla6^tm1Blw/J

Stock number: 005091
Product name: Nte-
Research areas: Neurobiology Research, Research Tools

Description

These Pnpla6 knock-out mice exhibit an embryonic lethal phenotype, and neuropathy target esterase activity in brain tissue is reduced.

Detailed description

Homozygous null mice have an embryonic lethal phenotype, failing to develop past embryonic day 8.5. Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and are more active than wildtype littermates. A reduced level of protein gene product is detected by immunoprecipitation and Western blot analysis of brain, testes and kidney, but protein levels are not reduced in liver. Beta galactosidase activity in heterozygotes aged embryonic day 13.5 is found in the developing lens and spinal cord. In adult heterozygotes, beta galactosidase activity is detected throughout the brain, especially in the cerebellar Purkinje cells and hippocampus. Beta galactosidase activity patterns mimic the endogenous gene expression pattern. NTE activity in brain tissue is reduced by 40%. Heterozygotes are more sensitive to organophosphate toxicity with increased motor activity and mortality. This mutant mouse strain may be useful in studies of neuropathological hyperactivity, Gulf War Syndrome, and organophosphate-induced sub-acute neurotoxicity.

Development

A targeting vector containing lacZ, neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 4 to 10. The lacZ coding sequence was inserted into exon 4, and exons 5 to 10 were deleted. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals from two independent ES cell clones were crossed. The offspring were mated to 129S1/SvImJ (STOCK#2448) mice.

Allele

Symbol: Pnpla6^tm1Blw
Name: targeted mutation 1, Carrolee Barlow
MGI accession ID: MGI:2655812
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Pnpla6
Marker name: patatin-like phospholipase domain containing 6
Chromosome: 8
Strain of origin: 129S6/SvEvTac
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: lacZ expression in heterozygotes at embryonic day 13.5 is found in the developing lens and spinal chord. In adults, beta-galgalactosidase is detected throughout the brain, especially in the cerebellar Purkinje cells and the hippocampus.
Molecular note: The gene was disrupted by an in-frame fusion of lacZ to exon 4 and replacement of exons 5-10 with a neomycin resistance gene.