Overview

Also Known As:Dgat-

These Dgat1 knock-out mice still synthesize triglycerides and exhibit resistance to diet-induced obesity.

Donating Investigator

Robert V Farese, Jr., Harvard University School of Public Health

Genetic overview

Genetic Background	Generation

Dgat1^tm1Far

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Dgat1	diacylglycerol O-acyltransferase 1

View Genetics

Research Applications

Cardiovascular Research
Internal/Organ Research
Metabolism Research
Developmental Biology Research
Diabetes and Obesity Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the Dgat1^tm1Far 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.

Development

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.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Smith SJ; Cases S; Jensen DR; Chen HC; Sande E; Tow B; Sanan DA; Raber J; Eckel RH; Farese RV Jr. 2000. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat [see comments] Nat Genet 25(1):87-90PubMed: 10802663 MGI: J:61885

View All References

Genetics

Dgat1^tm1Far

Allele Symbol: Dgat1^tm1Far

Allele Name	targeted mutation 1, Bob Farese
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

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Dgat1^tm1Far related

Cardiovascular Research
- Hypotriglyceridemia
Internal/Organ Research
- Adipose Defects
Metabolism Research
- Lipid Metabolism
Developmental Biology Research
- Skin and Hair Texture Defects
Diabetes and Obesity Research
- Obesity With Diabetes
  - diet-induced, resistant

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Dgat1^tm1Far/Dgat1^tm1Far
involves: 129S4/SvJae * C57BL/6J

adipose tissue phenotype

decreased percent body fat/body weight
- lower than Dgat1-sufficient mice

behavior/neurological phenotype

hyperactivity
- on the high-fat diet, mutant mice were twice as active as wild-type mice

integument phenotype

abnormal coat/ hair morphology

abnormal epidermal layer morphology

abnormal hair cycle

abnormal hair cycle anagen phase
- early entrance into second anagen
- prolonged first anagen

abnormal hair shedding
- increased shedding

abnormal skin condition

alopecia
- hair regrows but patchy alopecia always redevelops in variable locations and persists in 5 to 7 month old mice
- maintainance on a retinoid deficient diet prevents alopecia
- manifests as a prominent bald spot in the dorsal caudal region at 9 weeks

epidermal hyperplasia
- four days after a single application of retinol to shaved skin

lactation failure
- females had a complete absence of milk production

reddish skin
- due to three consecutive days of retinol application

scaly skin
- due to three consecutive days of retinol application

skin lesions
- cracking and crusty lesions
- due to three consecutive days of retinol application

sparse hair
- generalized hair thinning at 5 to 7 months of age

thick epidermis
- four days after a single application of retinol to shaved skin

endocrine/exocrine gland phenotype

lactation failure
- females had a complete absence of milk production

liver/biliary system phenotype

decreased liver cholesterol level
- after receiving a high-fat diet for 20 weeks, hepatic cholesterol ester levels are markedly reduced vs controls

decreased liver triglyceride level
- after receiving a high-fat diet for 20 weeks, hepatic triglyceride levels are markedly reduced vs controls

decreased susceptibility to hepatic steatosis
- when fed a high fat diet for 20 weeks, mice show significantly less hepatic steatosis vs wild-type controls

growth/size/body region phenotype

decreased body weight
- when Dgat1-deficient, Adipoq-sufficient mice are weaned onto a high-fat diet, they show decreased body weight over 20 weeks vs wild-type controls

decreased susceptibility to diet-induced obesity
- mice fed a chow diet had similar body weights, but the weight of the total fat pads in mutant mice was lower than control
- mutant mice has higher metabolic rates both on a chow diet and on a high-fat diet
- when fed a high-fat diet, mutant mice were resistant to obesity

homeostasis/metabolism phenotype

abnormal vitamin A level
- all trans retinoic acids in skin are increased 40%
- levels of unesterified retinol in skin are elevated 22% on a normal diet
- Normal - serum retinol and liver retinoid levels are normal

decreased circulating glucose level
- after high-fat diet for 8 weeks, mice have decreased blood glucose after an overnight fast vs controls

decreased circulating leptin level
- serum leptin levels are significantly lower than in Dgat1-sufficient animals regardless of Adipoq genotype (4.2 ng/ml vs ~17.7 ng/ml in Dgat1-suffcient)

decreased liver cholesterol level
- after receiving a high-fat diet for 20 weeks, hepatic cholesterol ester levels are markedly reduced vs controls

decreased liver triglyceride level
- after receiving a high-fat diet for 20 weeks, hepatic triglyceride levels are markedly reduced vs controls

decreased susceptibility to diet-induced obesity
- mice fed a chow diet had similar body weights, but the weight of the total fat pads in mutant mice was lower than control
- mutant mice has higher metabolic rates both on a chow diet and on a high-fat diet
- when fed a high-fat diet, mutant mice were resistant to obesity

improved glucose tolerance
- after glucose challenge, improved glucose tolerance compared to wild-type controls is seen; Dgat1-deficiency improves glucose tolerance by ~30-35% vs controls

increased insulin sensitivity
- tended to have lower glucose and insulin levels after a glucose tolerance test

increased oxygen consumption
- mice fed a higher fat diet have higher levels of oxygen consumption than Dgat1-sufficient mice

The following phenotype relates to a compound genotype created using this strain

Genotype: Dgat1^tm1Far/Dgat1^tm1Far
B6J.129S4-Dgat1

adipose tissue phenotype

decreased mammary fat pad weight
- the weights of mutant mammary fat pads are similar to those of wild-type mice during pregnancy, but are decreased at L1, probably due to lack of milk production

cellular phenotype

decreased mammary gland epithelial cell proliferation
- Normal - in contrast, levels of apoptosis remain similar to those of wild-type controls at P18, as shown by TUNEL staining
- on day 15 of pregnancy (P15), BrdU labeling shows a 40% reduction in proliferating nuclei in mutant mammary epithelium

integument phenotype

abnormal branching of the mammary ductal tree
- at P15, mutant mammary glands show a slight decrease in ductal structures
- Normal - however, ductal side branching appears normal at P8

abnormal mammary gland alveolus morphology
- by P18, mutant lobuloalveolar structures are less developed relative to wild-type controls
- Normal - however, formation of the initial alveolar buds appears normal at P8

abnormal mammary gland development
- whole wild-type mammary glands transplanted into mutant recipient mice show fully developed lobuloalveolar structures and visible milk droplets whereas whole mutant mammary glands transplanted into wild-type recipient mice fail to develop normally

abnormal mammary gland epithelium morphology
- female homozygotes show impaired differentiation of mammary gland epithelium in late pregnancy
- transplantation of mutant epithelium to wild-type mammary fat pads results in apparently normal epithelial growth, whereas transplantation of wild-type epithelium to mutant fat pads leads to underdeveloped and poorly differentiated epithelium

abnormal mammary gland growth during lactation
- on day 1 of lactation ( L1), mutant glands show a ~25% reduction in epithelial structures and a ~60% reduction in luminal expansion

abnormal milk composition
- Normal - in contrast, expression of beta-casein, an early differentiation marker, is similar to that in wild-type glands
- in mutant mammary glands, expression of whey acidic protein (WAP), a late differentiation marker, is absent at P18 and reduced at L1

decreased mammary gland epithelial cell proliferation
- Normal - in contrast, levels of apoptosis remain similar to those of wild-type controls at P18, as shown by TUNEL staining
- on day 15 of pregnancy (P15), BrdU labeling shows a 40% reduction in proliferating nuclei in mutant mammary epithelium

impaired mammary gland growth during pregnancy
- at P15, mutant mammary glands show a slight decrease in ductal structures, suggesting a developmental delay
- by P18, alveolar development is reduced and mutant glands show a ~25% reduction in epithelial structures and a ~60% reduction in luminal expansion

lactation failure
- Normal - however, pups fostered to lactating wild-type females suckle and develop normally
- milk production is totally absent, even after stimulation by oxytocin or by a second pregnancy
- pups born to female homozygotes die shortly after birth with no milk stripes in their stomachs

reproductive system phenotype

impaired mammary gland growth during pregnancy
- at P15, mutant mammary glands show a slight decrease in ductal structures, suggesting a developmental delay
- by P18, alveolar development is reduced and mutant glands show a ~25% reduction in epithelial structures and a ~60% reduction in luminal expansion

endocrine/exocrine gland phenotype

abnormal branching of the mammary ductal tree
- at P15, mutant mammary glands show a slight decrease in ductal structures
- Normal - however, ductal side branching appears normal at P8

abnormal mammary gland alveolus morphology
- by P18, mutant lobuloalveolar structures are less developed relative to wild-type controls
- Normal - however, formation of the initial alveolar buds appears normal at P8

abnormal mammary gland development
- whole wild-type mammary glands transplanted into mutant recipient mice show fully developed lobuloalveolar structures and visible milk droplets whereas whole mutant mammary glands transplanted into wild-type recipient mice fail to develop normally

abnormal mammary gland epithelium morphology
- female homozygotes show impaired differentiation of mammary gland epithelium in late pregnancy
- transplantation of mutant epithelium to wild-type mammary fat pads results in apparently normal epithelial growth, whereas transplantation of wild-type epithelium to mutant fat pads leads to underdeveloped and poorly differentiated epithelium

abnormal mammary gland growth during lactation
- on day 1 of lactation ( L1), mutant glands show a ~25% reduction in epithelial structures and a ~60% reduction in luminal expansion

abnormal milk composition
- Normal - in contrast, expression of beta-casein, an early differentiation marker, is similar to that in wild-type glands
- in mutant mammary glands, expression of whey acidic protein (WAP), a late differentiation marker, is absent at P18 and reduced at L1

decreased mammary gland epithelial cell proliferation
- Normal - in contrast, levels of apoptosis remain similar to those of wild-type controls at P18, as shown by TUNEL staining
- on day 15 of pregnancy (P15), BrdU labeling shows a 40% reduction in proliferating nuclei in mutant mammary epithelium

impaired mammary gland growth during pregnancy
- at P15, mutant mammary glands show a slight decrease in ductal structures, suggesting a developmental delay
- by P18, alveolar development is reduced and mutant glands show a ~25% reduction in epithelial structures and a ~60% reduction in luminal expansion

lactation failure
- Normal - however, pups fostered to lactating wild-type females suckle and develop normally
- milk production is totally absent, even after stimulation by oxytocin or by a second pregnancy
- pups born to female homozygotes die shortly after birth with no milk stripes in their stomachs

References

Smith SJ; Cases S; Jensen DR; Chen HC; Sande E; Tow B; Sanan DA; Raber J; Eckel RH; Farese RV Jr. 2000. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat [see comments] Nat Genet 25(1):87-90PubMed: 10802663 MGI: J:61885

Additional References

Graham KL; Werner BJ; Moyer KM; Patton AK; Krois CR; Yoo HS; Tverskoy M; LaJevic M; Napoli JL; Sobel RA; Zabel BA; Butcher EC. 2019. DGAT1 inhibits retinol-dependent regulatory T cell formation and mediates autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 116(8):3126-3135PubMed: 30718413 MGI: J:272992

Additional - Dgat1^tm1Far related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Dgat1
- Separated PCR:Dgat1
- Standard PCR:Dgat1
- Standard PCR:Dgat1
- Genotyping resources and troubleshooting
Breeding Considerations

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
- Additional Breeding and Husbandry Support
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Dgat1<tm1Far>

Related Products and Services

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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Also Known As:Dgat-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Dgat1tm1Far

Allele Symbol: Dgat1tm1Far

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Dgat1tm1Far related

Mammalian Phenotype Terms by Genotype

Genotype: Dgat1tm1Far/Dgat1tm1Farinvolves: 129S4/SvJae * C57BL/6J

adipose tissue phenotype

behavior/neurological phenotype

integument phenotype

endocrine/exocrine gland phenotype

liver/biliary system phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

Genotype: Dgat1tm1Far/Dgat1tm1FarB6J.129S4-Dgat1

adipose tissue phenotype

cellular phenotype

integument phenotype

reproductive system phenotype

endocrine/exocrine gland phenotype

References

Additional References

Additional - Dgat1tm1Far related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Dgat1^tm1Far

Allele Symbol: Dgat1^tm1Far

Genotype: Dgat1^tm1Far related

Genotype: Dgat1^tm1Far/Dgat1^tm1Far
involves: 129S4/SvJae * C57BL/6J

Genotype: Dgat1^tm1Far/Dgat1^tm1Far
B6J.129S4-Dgat1

Additional - Dgat1^tm1Far related