These Dgat1 knock-out mice still synthesize triglycerides and exhibit resistance to diet-induced obesity.
Robert V Farese, Jr., Harvard University School of Public Health
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Dgat1 | diacylglycerol O-acyltransferase 1 |
Mice homozygous for the Dgat1tm1Far targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities however, homozygous mutant females exhibit a complete absence of milk production, necessitating the use of foster mothers. Dgat1 mRNA is undetectable by Northern blot analysis, and DGAT enzyme activity in a variety of tissues is either absent or shows only residual levels. Surprisingly, in DGAT deficient mice triglyceride levels and fasting serum triglycerides levels are similar to wildtype controls. Although homozygotes do not differ in body weight compared to age- and sex-matched controls, total fat pad weight is reduced. Tissue triglyceride levels are reduced 30-40% in white adipose tissue and muscle. Liver triglyceride levels tend to be lower in chow-fed DGAT-deficient mice, but high-fat feeding leads to significantly lower liver triglycerides. Changes in tissue triglyceride levels are associated with increased sensitivity to insulin and leptin. Additionally, infusion of leptin suppresses weight gain significantly more in DGAT-deficient mice compared to controls. Dry fur and hair loss in mutant mice are evident by 6-8 weeks, resulting from sebaceous gland atrophy and abnormal fur lipid production (especially type 2 wax diesters). DGAT-deficient mice also exhibit impaired water repulsion and hypothermia after water immersion. Interestingly, leptin modulates the fur and skin effects seen with DGAT deficiency. Homozygotes that are maintained on a high fat diet (21% fat by weight) are resistant to obesity. Resistance to diet-induced obesity is attributed to increased energy expenditure in Dgat1-null mice. This mutant strain is a suitable tool for use in studies examining mechanisms of triglyceride synthesis and the relationship between triglyceride synthesis and obesity, leptin, and insulin resistance. DGAT-deficient mice also provide a useful model to study the role of DGAT in fur and sebaceous gland physiology.
A targeting vector containing a neomycin resistance gene was used to disrupt a portion of the Dgat1 gene that encodes the carboxy-terminal 27% of the protein product. The construct was transfected into 129S4/SvJae derived RF8 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J mice.
Allele Name | targeted mutation 1, Bob Farese |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | |
Gene Symbol and Name | Dgat1, diacylglycerol O-acyltransferase 1 |
Gene Synonym(s) | |
Strain of Origin | 129S4/SvJae |
Chromosome | 15 |
Molecular Note | A genomic fragment containing sequences encoding the carboxy-terminus of the protein was replaced by a neomycin cassette. Northern blot analysis did not detect a full length transcript produced from this allele in homozygous mice. Tissue DGAT activity was absent ot severely reduced in homozygous mice. |
Mutations Made By | Robert Farese, Jr., Harvard University School of Public Health |
This strain originated on a B6;129S4 background and has been backcrossed to C57BL/6J for ten generations. If homozygous females are used for breeding, foster mothers are necessary, as homozygous females are unable to nurse. The donating investigator maintained this mutant strain by crossing homozygous males with heterozygous females. Coat color expected from breeding:Black
When using the Dgat- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003824 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Dgat1<tm1Far> |
Frozen Mouse Embryo | B6.129S4-Dgat1<tm1Far>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129S4-Dgat1<tm1Far>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129S4-Dgat1<tm1Far>/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | B6.129S4-Dgat1<tm1Far>/J Frozen Embryos | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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