Homozygous Dgat2tm1Far mice exhibit perinatal lethality and newborns are hypoglycemic and lipopenic, exhibiting reduced plasma triglyceride, free fatty acid and glucose levels and have almost no white fat tissue.
Robert V Farese, Jr., Harvard University School of Public Health
Mice that are homozygous for the targeted mutation have a perinatal lethal phenotype, most fail to survive past 6 hours after birth due to dehydration, skin barrier abnormalities, hypothermia and energy deficiencies. Reduced levels of gene product (mRNA) are detected by RT-PCR analysis of brown adipose tissue and livers of neonate homozygous mutants. Growth retardation is observed in homozygous embryos after embryonic day 12.5. Newborn homozygotes are hypoglycemic and lipopenic, exhibiting reduced plasma triglyceride, free fatty acid and glucose levels and have almost no white fat tissue. Within a few hours of birth, the skin of homozygotes becomes dry and cracked. Homozygous mutants rapidly lose weight due to dehydration caused by impaired permeability barrier function. Histological analysis of skin tissue from homozygotes reveals abnormally thin epidermis and compact orthohyperkeratosis of the stratum corneum. Homozygotes surviving between 8 and 24 hours develop tail necrosis. Heterozygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This mutant mouse strain may be useful in studies of embryonic development, essential fatty acid and triglyceride metabolism.
A targeting vector containing a floxed neo cassette and a herpes simplex virus thymidine kinase gene was used to disrupt exons 3 and 4. The construct was electroporated into 129S4/SvJae embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to the same for 8 generations.
|Allele Name||targeted mutation 1, Bob Farese|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Dgat2-; Dgat2tm1Rvf|
|Gene Symbol and Name||Dgat2, diacylglycerol O-acyltransferase 2|
|Strain of Origin||129S4/SvJae|
|Molecular Note||The replacement of highly conserved exons 3 and 4 with a floxed neo cassette via homologous recombination introduces a premature stop codon. The encoded protein would be severely truncated (112 amino acids compared to 387), including 29 new amino acids. Homozygous mutant liver showed that diacylglycerol acyltransferase activity was reduced by 53%.|
|Mutations Made By|| |
Scot Stone, Gladstone Institutes
When maintaining a live colony, these mice are bred as heterozygotes due to homozygous perinatal lethal phenotype.
When using the DGAT2 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #005951 in your Materials and Methods section.
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