Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation >N8+N1p   Donating Investigator Bob Farese,   Gladstone Inst of Cardiovascular Disease

Description
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.

Development
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.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Dgat2^tm1Rvf/Dgat2^tm1Rvf

        involves: 129S4/SvJae * C57BL/6J

• lethality-prenatal/perinatal
• neonatal lethality (MGI Ref ID J:88742)
  • mice die 2 to 24 hours after birth, putatively due to inadequate substrates for energy metabolism and impaired permeability barrier function in the skin
  • subcutaneous injections of glucose at birth prolongs life for only a few hours
  • subcutaneous injections of saline combined with increasing the ambient humidity from 50 to 85% prolongs life for several hours
• growth/size phenotype
• decreased body size (MGI Ref ID J:88742)
  • reduced size persists after birth
• decreased body length (MGI Ref ID J:88742)
  • mutants are 15% shorter than wild-type
• decreased body weight (MGI Ref ID J:88742)
  • newborns weigh 20% less than wild-type
• weight loss (MGI Ref ID J:88742)
  • newborns rapidly lose weight due to increased permeability of skin and consequent fluid loss
• reduced fetal size (MGI Ref ID J:88742)
  • 14% reduction in body weight at E18.5
  • however, body weight at E12.5 is similar to wild-type
• homeostasis/metabolism phenotype
• abnormal lipid level (MGI Ref ID J:88742)
  • reduction in neutral lipid content in the liver and BAT
  • content of the skin lipid acylceramide is reduced by more than 60%
• abnormal phospholipid level (MGI Ref ID J:88742)
  • neonatal skin shows a moderate reduction in phosphatidylcholine
• decreased circulating free fatty acid level (MGI Ref ID J:88742)
  • 70-90% lower in newborns
• decreased fatty acid level (MGI Ref ID J:88742)
  • all fatty acid classes are reduced by more than 95% in livers
  • free fatty acid levels are reduced in total carcass and in liver
• decreased unsaturated fatty acid level (MGI Ref ID J:88742)
  • content of linoleic acid in free fatty acids in both liver and plasma is reduced 77 and 85%, respectively, and by 60% in cholesterol esters in the liver
  • however, phospholipids of livers have similar levels of linoleic acid as wild-type
  • reduction in the linoleic acid content of triglycerides and free fatty acids in the skin
• decreased triglyceride level (MGI Ref ID J:88742)
  • 86% reduction in tissue triglycerides at E12.5
  • 93% and 60% reduction in total carcass and BAT triglyceride content, respectively
  • triglyceride content is nearly undetectable in fetal and newborn livers
  • lipids of neonatal skin show a 96% reduction in triglyceride content
• decreased circulating triglyceride level (MGI Ref ID J:88742)
  • 70-90% lower in newborns
• decreased body temperature (MGI Ref ID J:88742)
  • lower surface body temperature
• decreased glycogen level (MGI Ref ID J:88742)
  • after birth, hepatic glycogen levels decrease and are 67% lower than in wild-type
• dehydration (MGI Ref ID J:88742)
• hypoglycemia (MGI Ref ID J:88742)
  • 70-90% lower in newborns
  • plasma glucose levels are reduced by 68% in E18.5 mutants
• impaired skin barrier function (MGI Ref ID J:88742)
  • skin barrier abnormalities, resulting in dehydration from increased epidermal permeability
• skin/coat/nails phenotype
• abnormal epidermal layer morphology (MGI Ref ID J:88742)
  • effacement of the epidermal rete ridges/papillary projections, leading to a flattened dermo-epidermal interface
• abnormal cornified layer morphology (MGI Ref ID J:88742)
  • the epidermis has reduced numbers of lamellar membranes in the stratum corneum extracellular spaces
  • individual lamellar bodies often lack normal contents
• hyperkeratosis (MGI Ref ID J:88742)
  • compact orthohyperkeratosis of affected stratum corneum
• thin epidermis (MGI Ref ID J:88742)
• dry skin (MGI Ref ID J:88742)
  • within a few hours after birth, skin appears dry and cracked
• impaired skin barrier function (MGI Ref ID J:88742)
  • skin barrier abnormalities, resulting in dehydration from increased epidermal permeability
• shiny skin (MGI Ref ID J:88742)
• tight skin (MGI Ref ID J:88742)
  • skin lacks elasticity
• limbs/digits/tail phenotype
• abnormal tail morphology (MGI Ref ID J:88742)
  • necrosis of the tail develops in mutants that survive for 8-24 hours
• behavior/neurological phenotype
• abnormal suckling behavior (MGI Ref ID J:88742)
  • mutants rarely suckle

View Research Applications

Research Applications

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

Cardiovascular Research
Hypotriglyceridemia
Other (altered fat metabolism)

Dermatology Research
Skin and Hair Texture Defects

Developmental Biology Research
Growth Defects Growth Defects (homozygous)
Perinatal Lethality (Homozygous)
Skin and Hair Texture Defects

Diabetes and Obesity Research
Hypoglycemia

Metabolism Research
Lipid Metabolism

Genes & Alleles

Gene & Allele Information

Allele Symbol		Dgat2tm1Rvf
Allele Name		targeted mutation 1, Robert V Farese
Allele Type		Targeted (knock-out)
Common Name(s)		Dgat2-;
Mutation Made By		Scot Stone,   Gladstone Institutes
Strain of Origin		129S4/SvJae
ES Cell Line Strain		129
Gene Symbol and Name		Dgat2, diacylglycerol O-acyltransferase 2
Chromosome		7
Gene Common Name(s)		0610010B06Rik; DKFZp686A15125; HMFN1045; MGC108863; RIKEN cDNA 0610010B06 gene;
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%. [MGI Ref ID J:88742]

Genotyping

Genotyping Information

Genotyping Protocols

Dgat2^tm1Rvf, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Stone SJ; Myers HM; Watkins SM; Brown BE; Feingold KR; Elias PM; Farese RV Jr. 2004. Lipopenia and skin barrier abnormalities in DGAT2-deficient mice. J Biol Chem 279(12):11767-76. [PubMed: 14668353]  [MGI Ref ID J:88742]

Additional References

Dgat2^tm1Rvf related

Man WC; Miyazaki M; Chu K; Ntambi J. 2006. Colocalization of SCD1 and DGAT2: implying preference for endogenous monounsaturated fatty acids in triglyceride synthesis. J Lipid Res 47(9):1928-39. [PubMed: 16751624]  [MGI Ref ID J:114482]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as heterozygotes due to homozygous perinatal lethal phenotype.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

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.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.