Ppara deficient mutant mice exhibit increased gonadal adipose tissue stores, abnormal epidermal development and delayed wound healing. This mutant mouse strain may be useful in studies of lipid metabolism, cell proliferation, diabetes, obesity, and wound healing.
Frank J Gonzalez, National Institutes of Health (NIH/NCI)
Mice homozygous for the targeted mutation are viable and fertile. An altered response to a group of compounds (peroxisome proliferators) that induce peroxisome proliferation and hepatocarcinogenesis is observed. No peroxisome proliferation response is detected when these mice are challenged with classical peroxisome proliferators. Typically, such a response includes hepatomegaly, peroxisome proliferation and transcriptional activation of a set of target enzyme genes. Accumulation of lipid droplets observed in liver tissue suggests that Ppara is involved in maintaining the homeostasis of hepatic lipid metabolism. Homozygotes exhibit increased gonadal adipose tissue stores, abnormal epidermal development and delayed wound healing. This mutant mouse strain may be useful in studies of lipid metabolism, cell proliferation, diabetes, obesity, and wound healing.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 8, which encodes the ligand binding domain. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6N blastocysts. The mice were initially maintained on a 129S4/SvJae background, and then were backcrossed for 10 generations on to the C57BL/6J background (please see note about SNP analysis below). Heterozygotes were then intercrossed to generate homozygotes. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
A 27 SNP (single nucleotide polymorphism) panel analysis performed by The Jackson Laboratory revealed 3 of 27 markers (on chromsomes 3, 12 and 15) that were not C57BL/6 allele-type. These markers are 129S4/SvJae allele-type and suggest the strain was not completely backcrossed prior to arrival at The Jackson Laboratory.
|Allele Name||targeted mutation 1, Frank J Gonzalez|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||mPPARalpha-; PPAR-alpha-; PPARalpha-; PPARalpha-null; PparatniJGonz|
|Gene Symbol and Name||Ppara, peroxisome proliferator activated receptor alpha|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin resistance cassette replaced 83 bp of the coding sequence in exon 8. Northern blot analysis did not detect a transcript of wild-type size on RNA derived from liver of homozygous mice. An larger abnormal transcript was detected. Western blot analysis did not detect PPARA protein in extracts derived from livers of homozygous mice.|
|Mutations Made By|| |
Christopher Coakley, Laboratory of Metabolism, NCI
When maintaining a live colony, these mice can be bred as homozygotes.
When using the mPPARα- mouse strain in a publication, please cite the originating article(s) and include JAX stock #008154 in your Materials and Methods section.