This knockout mutation of the Mogat2 gene displays resistance to high fat diet-induced obesity, glucose intolerance, hypercholesterolemia and fatty liver and may be useful in studies of obesity, fat absorption and energy homeostasis.
Robert V Farese, Jr., Harvard University School of Public Health
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. On a high fat diet, homozygotes exhibit resistance to obesity, glucose intolerance, hypercholesterolemia and fatty liver. For example, after 16 weeks of feeding on a 60 kcal% fat diet, male mice gain 40% less weight and have a 50% lower fat mass than wild type mice. Female mice exhibit similar resistance. Heterozygotes have an intermediate phenotype. After 2 months on high fat diet, male mice have lower fasting insulin concentrations, better glucose tolerance, lower total and non-HLD cholesterol, and are resistance to hepatic steatosis. Although food consumption and dietary fat absorption are similar in wild-type and mutant mice, entry of dietary fat into the circulation occurs at a reduced rate.
This mutant mouse strain may be useful in studies of obesity, fat absorption and energy homeostasis.
A targeting vector containing herpes simplex virus thymidine kinase and neomycin resistance genes was used to replace exon 1, which includes the translation-initiating methionine. The construct was electroporated into 129S4/SvJae derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The donating investigator reported that the resulting chimeric animals were crossed to C57BL/6J for at least 12 generations (see SNP note below). Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Bob Farese|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Mogat2, monoacylglycerol O-acyltransferase 2|
|Strain of Origin||129S4/SvJae|
|Molecular Note||Exon 1 was replaced with a neo cassette. The absence of protein expression was confirmed by western blot analysis on intestinal extracts.|
|Mutations Made By|| |
Robert Farese, Jr., Harvard University School of Public Health
While maintaining a live colony, these mice are bred as heterozygotes.
When using the B6.129S4-Mogat2tm1Far/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #011085 in your Materials and Methods section.