Description

Strain Information

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

Description
Mice that are homozygous null for the Ttpa gene are viable, normal in size and do not display any gross physical abnormalities. The Ttpa protein product is required for the maintenance of proper alpha-tocopherol levels, the major form of vitamin E in plasma and tissues. The absence of Ttpa protein product in homozygous-null animals results in a corresponding 95% reduction in alpha-tocopherol. Low levels of alpha-tocopherol render female mice infertile, a condition that can be addressed with vitamin E supplements. Male fertility is unimpaired. These mice provide a viable model for studying vitamin E deficiency.

Development
A targeting vector containing thymidine kinase, lacZ and neomycin resistance genes was used to disrupt the Ttpa exons 1 and 2. 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 Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Vitamin E, Familial Isolated Deficiency Of; VED - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

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.

Ttpa^tm1Far/Ttpa⁺

        involves: 129S4/SvJae * C57BL/6

• homeostasis/metabolism phenotype
• abnormal fat-soluble vitamin level (MGI Ref ID J:66419)
  • chow-fed heterozygotes exhibit a ~50% reduction of alpha-tocopherol levels in plasma and most tissues

Ttpa^tm1Far/Ttpa^tm1Far

        involves: 129S4/SvJae * C57BL/6

• homeostasis/metabolism phenotype
• abnormal fat-soluble vitamin level (MGI Ref ID J:66419)
  • homozygotes are viable, healthy and show no obvious neurological abnormalities, such as ataxia, up to 18 months of age
  • however, chow-fed homozygotes exhibit a >90% reduction of alpha-tocopherol levels in plasma and most tissues
  • notably, in liver, adipose tissue, adrenal gland, and aorta, alpha-tocopherol levels are only 15-35% of wild-type levels
• reproductive system phenotype
• female infertility (MGI Ref ID J:66419)
  • female homozygotes are infertile whereas male homozygotes exhibit normal fertility
  • vitamin E supplementation (1,000 units/kg of diet) completely reverses the fertility defect in female mutants
• cardiovascular system phenotype
• *normal* cardiovascular system phenotype (MGI Ref ID J:66419)
  • normolipidemic homozygotes exhibit no spontaneous atherosclerosis; however, vitamin E deficiency appears to increase the severity of atherosclerotic lesions in a atherosclerosis-susceptible setting e.g. Apoe deficiency

View Research Applications

Research Applications

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

Ttpa^tm1Far related

Cardiovascular Research
Atherosclerosis

Developmental Biology Research
Embryonic Lethality (Homozygous)

Metabolism Research
Lipid Metabolism

Neurobiology Research
Neuromuscular Defects

Reproductive Biology Research
Fertility Defects (females only)

Research Tools
Apoptosis Research
Cancer Research
Dermatology Research
Immunology and Inflammation Research
Metabolism Research
Neurobiology Research
Reproductive Biology Research
Sensorineural Research

Sensorineural Research
Retinal Degeneration

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ttpatm1Far
Allele Name		targeted mutation 1, Robert V Farese
Allele Type		Targeted (Reporter)
Common Name(s)		Ttpa-; alpha-TTP-KO;
Mutation Made By		Bob Farese,   Gladstone Inst of Cardiovascular Disease
Strain of Origin		129S4/SvJae
ES Cell Line Name		RF8
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Ttpa, tocopherol (alpha) transfer protein
Chromosome		4
Gene Common Name(s)		ATTP; AVED; TTP; TTP1; alpha TTP; alpha-TTP; alphaTTP;
Molecular Note		Insertion of a lacZ-neomycin resistance cassette into the 5' untranslated region in exon 1 deleted the translational start codon. Immunoblot analysis of liver did not detect wild-type protein in homozygous mutant mice. [MGI Ref ID J:66419]

Genotyping

Genotyping Information

Genotyping Protocols

Ttpa^tm1Far, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Ttpa^tm1Far related

Gohil K; Oommen S; Quach HT; Vasu VT; Aung HH; Schock B; Cross CE; Vatassery GT. 2008. Mice lacking alpha-tocopherol transfer protein gene have severe alpha-tocopherol deficiency in multiple regions of the central nervous system. Brain Res 1201:167-76. [PubMed: 18299118]  [MGI Ref ID J:135694]

Gohil K; Schock BC; Chakraborty AA; Terasawa Y; Raber J; Farese RV Jr; Packer L; Cross CE; Traber MG. 2003. Gene expression profile of oxidant stress and neurodegeneration in transgenic mice deficient in alpha-tocopherol transfer protein. Free Radic Biol Med 35(11):1343-54. [PubMed: 14642382]  [MGI Ref ID J:132440]

Suarna C; Wu BJ; Choy K; Mori T; Croft K; Cynshi O; Stocker R. 2006. Protective effect of vitamin E supplements on experimental atherosclerosis is modest and depends on preexisting vitamin E deficiency. Free Radic Biol Med 41(5):722-30. [PubMed: 16895792]  [MGI Ref ID J:111987]

Terasawa Y; Ladha Z; Leonard SW; Morrow JD; Newland D; Sanan D; Packer L; Traber MG; Farese RV Jr. 2000. Increased atherosclerosis in hyperlipidemic mice deficient in alpha -tocopherol transfer protein and vitamin E Proc Natl Acad Sci U S A 97(25):13830-4. [PubMed: 11095717]  [MGI Ref ID J:66419]

Traber MG; Siddens LK; Leonard SW; Schock B; Gohil K; Krueger SK; Cross CE; Williams DE. 2005. Alpha-tocopherol modulates Cyp3a expression, increases gamma-CEHC production, and limits tissue gamma-tocopherol accumulation in mice fed high gamma-tocopherol diets. Free Radic Biol Med 38(6):773-85. [PubMed: 15721988]  [MGI Ref ID J:98008]

Vasu VT; Hobson B; Gohil K; Cross CE. 2007. Genome-wide screening of alpha-tocopherol sensitive genes in heart tissue from alpha-tocopherol transfer protein null mice (ATTP(-/-)). FEBS Lett 581(8):1572-8. [PubMed: 17382327]  [MGI Ref ID J:121429]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6;129S background and has been backcrossed to C57BL/6J for ten generations before being made homozygous. Homozygous females are infertile due to a vitamin E deficiency. Males have no fertility problems. The donating investigator maintains these mice by crossing homozygous males with heterozygous females.
Diet Information	LabDiet® 5K52/5K67

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

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. 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. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
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
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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

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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.

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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.

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