Strain Name:

B6;129S-Mttptm2Sgy/J

Stock Number:

003902

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Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating InvestigatorDr. Stephen Young,   Gladstone Institutes UCSF

Description
These mice possess loxP sites located 2.5 kb 5' of exon 1 and flanking a neomycin resistance gene inserted into intron 1 of the Mttp gene. Mice that are homozygous for this floxed Mttp allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.
When bred to a strain expressing interferon inducible Cre recombinase in liver tissue (see Stock No. 003556 for example), this mutant mouse strain may be useful in lipoprotein research.

Development
A targeting vector containing Mttp sequence, neomycin resistance and herpes simplex virus thymidine kinase genes was utilized in the construction of this mutant. Similarly oriented loxP sites were placed 2.5 kb upstream of exon 1 and flanking the neomycin resistance gene (located in intron 1). The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Mice harboring the mutant allele were obtained and bred to homozygosity.

Related Strains

Strains carrying   Mttptm2Sgy allele
004192   STOCK Mttptm2Sgy Ldlrtm1Her Apobtm2Sgy Tg(Mx1-cre)1Cgn/J
View Strains carrying   Mttptm2Sgy     (1 strain)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Abdominal Obesity-Metabolic Syndrome 1; AOMS1   (MTTP)
Abetalipoproteinemia; ABL   (MTTP)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Mttptm2Sgy/Mttptm2Sgy Tg(Mx1-cre)1Cgn/Tg(Mx1-cre)1Cgn

        involves: 129S4/SvJae * C57BL/6 * CBA   (conditional)
  • homeostasis/metabolism phenotype
  • abnormal circulating protein level
    • following polyIC induction, plasma apoB-100 levels are not detectable   (MGI Ref ID J:83459)
    • following polyIC induction, plasma apoB-48 levels are reduced by ~65%   (MGI Ref ID J:83459)
  • decreased circulating cholesterol level
    • following induction of cre expression with polyIC, plasma cholesterol levels are reduced by 60%   (MGI Ref ID J:83459)
    • decreased circulating HDL cholesterol level
      • following polyIC induction, plasma HDL levels are reduced by 50%   (MGI Ref ID J:83459)
    • decreased circulating LDL cholesterol level
      • following polyIC induction, plasma IDL and LDL levels are almost undetectable   (MGI Ref ID J:83459)
    • decreased circulating VLDL cholesterol level
      • following polyIC induction, plasma VLDL levels are almost undetectable   (MGI Ref ID J:83459)
  • decreased circulating triglyceride level
    • following polyIC induction, plasma triglyceride levels are reduced by 45%   (MGI Ref ID J:83459)
  • increased liver cholesterol level
    • following polyIC induction, hepatic cholesterol levels are increased by 65%   (MGI Ref ID J:83459)
  • increased liver triglyceride level
    • following polyIC induction, hepatic triglyceride levels are increased 2.5-fold   (MGI Ref ID J:83459)
  • liver/biliary system phenotype
  • abnormal liver physiology
    • following polyIC induction, apoB-100 is nearly absent in hepatic microsomes while apoB-48 remains unaffected   (MGI Ref ID J:83459)
    • following polyIC induction, no changes are observed in the levels of microsomal luminal chaparone proteins or cytosolic heat shock proteins   (MGI Ref ID J:83459)
    • following polyIC induction, hepatic secretion of apoB-100 is blocked without causing apoB to accumulate in the hepatic ER   (MGI Ref ID J:83459)
  • increased liver cholesterol level
    • following polyIC induction, hepatic cholesterol levels are increased by 65%   (MGI Ref ID J:83459)
  • increased liver triglyceride level
    • following polyIC induction, hepatic triglyceride levels are increased 2.5-fold   (MGI Ref ID J:83459)
  • increased liver weight
    • following polyIC induction, mutant liver weights are increased while body weights remain normal   (MGI Ref ID J:83459)
View Research Applications

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

Research Tools
Cre-lox System
      loxP-flanked Sequences
Genetics Research
      Mutagenesis and Transgenesis
      Mutagenesis and Transgenesis: Cre-lox System

Mttptm2Sgy related

Metabolism Research
Lipid Metabolism

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Mttptm2Sgy
Allele Name targeted mutation 2, Steven G Young
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) Mttpfl;
Mutation Made ByDr. Stephen Young,   Gladstone Institutes UCSF
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Site of Expressioncre mutation deletes floxed Mttp gene, reversing hypercholesterolemia phenotype
Gene Symbol and Name Mttp, microsomal triglyceride transfer protein
Chromosome 3
Gene Common Name(s) 1810043K16Rik; ABL; MTP; RIKEN cDNA 1810043K16 gene;
Molecular Note A neomycin resistance cassette flanked by loxP sites was inserted into intron 1. An additional loxP site was inserted 2.5 kb upstream of the promoter and exon 1. [MGI Ref ID J:54612]

Genotyping

Genotyping Information


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Raabe M; Veniant MM; Sullivan MA; Zlot CH; Bjorkegren J; Nielsen LB; Wong JS; Hamilton RL; Young SG. 1999. Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice. J Clin Invest 103(9):1287-98. [PubMed: 10225972]  [MGI Ref ID J:54612]

Additional References

Mttptm2Sgy related

Amigo L; Castro J; Miquel JF; Zanlungo S; Young S; Nervi F. 2006. Inactivation of hepatic microsomal triglyceride transfer protein protects mice from diet-induced gallstones. Gastroenterology 131(6):1870-8. [PubMed: 17064699]  [MGI Ref ID J:124954]

Anwar K; Iqbal J; Hussain MM. 2007. Mechanisms involved in vitamin E transport by primary enterocytes and in vivo absorption. J Lipid Res 48(9):2028-38. [PubMed: 17582142]  [MGI Ref ID J:125237]

Bartels ED; Nielsen JM; Hellgren LI; Ploug T; Nielsen LB. 2009. Cardiac expression of microsomal triglyceride transfer protein is increased in obesity and serves to attenuate cardiac triglyceride accumulation. PLoS ONE 4(4):e5300. [PubMed: 19390571]  [MGI Ref ID J:148263]

Bjorkegren J; Beigneux A; Bergo MO; Maher JJ; Young SG. 2002. Blocking the secretion of hepatic very low density lipoproteins renders the liver more susceptible to toxin-induced injury. J Biol Chem 277(7):5476-83. [PubMed: 11739387]  [MGI Ref ID J:74633]

Bjorkegren J; Veniant M; Kim SK; Withycombe SK; Wood PA; Hellerstein MK; Neese RA; Young SG. 2001. Lipoprotein secretion and triglyceride stores in the heart. J Biol Chem 276(42):38511-7. [PubMed: 11481337]  [MGI Ref ID J:120416]

Bjorkegren JL; Hagg S; Talukdar HA; Foroughi Asl H; Jain RK; Cedergren C; Shang MM; Rossignoli A; Takolander R; Melander O; Hamsten A; Michoel T; Skogsberg J. 2014. Plasma cholesterol-induced lesion networks activated before regression of early, mature, and advanced atherosclerosis. PLoS Genet 10(2):e1004201. [PubMed: 24586211]  [MGI Ref ID J:211003]

Bravo I; Amigo L; Cohen DE; Nervi F; Rigotti A; Francone O; Zanlungo S. 2007. Role of plasma and liver cholesterol- and lipoprotein-metabolism determinants in LpX formation in the mouse. Biochim Biophys Acta 1770(6):979-88. [PubMed: 17399905]  [MGI Ref ID J:121757]

Dikkers A; Annema W; de Boer JF; Iqbal J; Hussain MM; Tietge UJ. 2014. Differential impact of hepatic deficiency and total body inhibition of MTP on cholesterol metabolism and RCT in mice. J Lipid Res 55(5):816-25. [PubMed: 24511105]  [MGI Ref ID J:210163]

Dominguez JA; Xie Y; Dunne WM; Yoseph BP; Burd EM; Coopersmith CM; Davidson NO. 2012. Intestine-specific Mttp deletion decreases mortality and prevents sepsis-induced intestinal injury in a murine model of Pseudomonas aeruginosa pneumonia. PLoS One 7(11):e49159. [PubMed: 23145105]  [MGI Ref ID J:194796]

Dougan SK; Rava P; Hussain MM; Blumberg RS. 2007. MTP regulated by an alternate promoter is essential for NKT cell development. J Exp Med 204(3):533-45. [PubMed: 17312007]  [MGI Ref ID J:125365]

Feig JE; Parathath S; Rong JX; Mick SL; Vengrenyuk Y; Grauer L; Young SG; Fisher EA. 2011. Reversal of hyperlipidemia with a genetic switch favorably affects the content and inflammatory state of macrophages in atherosclerotic plaques. Circulation 123(9):989-98. [PubMed: 21339485]  [MGI Ref ID J:183750]

Iqbal J; Rudel LL; Hussain MM. 2008. Microsomal triglyceride transfer protein enhances cellular cholesteryl esterification by relieving product inhibition. J Biol Chem 283(29):19967-80. [PubMed: 18502767]  [MGI Ref ID J:138737]

Khatun I; Zeissig S; Iqbal J; Wang M; Curiel D; Shelness GS; Blumberg RS; Hussain MM. 2012. Phospholipid transfer activity of microsomal triglyceride transfer protein produces apolipoprotein B and reduces hepatosteatosis while maintaining low plasma lipids in mice. Hepatology 55(5):1356-68. [PubMed: 22121032]  [MGI Ref ID J:210793]

Larsson SL; Skogsberg J; Bjorkegren J. 2004. The low density lipoprotein receptor prevents secretion of dense apoB100-containing lipoproteins from the liver. J Biol Chem 279(2):831-6. [PubMed: 14583618]  [MGI Ref ID J:124544]

Liao W; Hui TY; Young SG; Davis RA. 2003. Blocking microsomal triglyceride transfer protein interferes with apoB secretion without causing retention or stress in the ER. J Lipid Res 44(5):978-85. [PubMed: 12588952]  [MGI Ref ID J:83459]

Lieu HD; Withycombe SK; Walker Q; Rong JX; Walzem RL; Wong JS; Hamilton RL; Fisher EA; Young SG. 2003. Eliminating atherogenesis in mice by switching off hepatic lipoprotein secretion. Circulation 107(9):1315-21. [PubMed: 12628954]  [MGI Ref ID J:91722]

Miller JD; Weiss RM; Serrano KM; Brooks RM 2nd; Berry CJ; Zimmerman K; Young SG; Heistad DD. 2009. Lowering plasma cholesterol levels halts progression of aortic valve disease in mice. Circulation 119(20):2693-701. [PubMed: 19433756]  [MGI Ref ID J:166428]

Miller JD; Weiss RM; Serrano KM; Castaneda LE; Brooks RM; Zimmerman K; Heistad DD. 2010. Evidence for active regulation of pro-osteogenic signaling in advanced aortic valve disease. Arterioscler Thromb Vasc Biol 30(12):2482-6. [PubMed: 20864669]  [MGI Ref ID J:183146]

Minehira K; Young SG; Villanueva CJ; Yetukuri L; Oresic M; Hellerstein MK; Farese RV Jr; Horton JD; Preitner F; Thorens B; Tappy L. 2008. Blocking VLDL secretion causes hepatic steatosis but does not affect peripheral lipid stores or insulin sensitivity in mice. J Lipid Res 49(9):2038-44. [PubMed: 18515909]  [MGI Ref ID J:139765]

Minehira-Castelli K; Leonard SW; Walker QM; Traber MG; Young SG. 2006. Absence of VLDL secretion does not affect alpha-tocopherol content in peripheral tissues. J Lipid Res 47(8):1733-8. [PubMed: 16710047]  [MGI Ref ID J:112587]

Parathath S; Grauer L; Huang LS; Sanson M; Distel E; Goldberg IJ; Fisher EA. 2011. Diabetes adversely affects macrophages during atherosclerotic plaque regression in mice. Diabetes 60(6):1759-69. [PubMed: 21562077]  [MGI Ref ID J:177946]

Sagiv Y; Bai L; Wei DG; Agami R; Savage PB; Teyton L; Bendelac A. 2007. A distal effect of microsomal triglyceride transfer protein deficiency on the lysosomal recycling of CD1d. J Exp Med 204(4):921-8. [PubMed: 17403933]  [MGI Ref ID J:125608]

Skogsberg J; Dicker A; Ryden M; Astrom G; Nilsson R; Bhuiyan H; Vitols S; Mairal A; Langin D; Alberts P; Walum E; Tegner J; Hamsten A; Arner P; Bjorkegren J. 2008. ApoB100-LDL acts as a metabolic signal from liver to peripheral fat causing inhibition of lipolysis in adipocytes. PLoS ONE 3(11):e3771. [PubMed: 19020660]  [MGI Ref ID J:143905]

Skogsberg J; Lundstrom J; Kovacs A; Nilsson R; Noori P; Maleki S; Kohler M; Hamsten A; Tegner J; Bjorkegren J. 2008. Transcriptional profiling uncovers a network of cholesterol-responsive atherosclerosis target genes. PLoS Genet 4(3):e1000036. [PubMed: 18369455]  [MGI Ref ID J:136835]

Xie Y; Fung HY; Newberry EP; Kennedy S; Luo J; Crooke RM; Graham MJ; Davidson NO. 2014. Hepatic Mttp deletion reverses gallstone susceptibility in L-Fabp knockout mice. J Lipid Res 55(3):540-8. [PubMed: 24474819]  [MGI Ref ID J:208783]

Xie Y; Luo J; Kennedy S; Davidson NO. 2007. Conditional intestinal lipotoxicity in Apobec-1-/- Mttp-IKO mice: a survival advantage for mammalian intestinal apolipoprotein BmRNA editing. J Biol Chem 282(45):33043-51. [PubMed: 17855359]  [MGI Ref ID J:126942]

Xie Y; Matsumoto H; Nalbantoglu I; Kerr TA; Luo J; Rubin DC; Kennedy S; Davidson NO. 2013. Intestine-Specific Mttp Deletion Increases the Severity of Experimental Colitis and Leads to Greater Tumor Burden in a Model of Colitis Associated Cancer. PLoS One 8(6):e67819. [PubMed: 23805328]  [MGI Ref ID J:204352]

Xie Y; Newberry EP; Young SG; Robine S; Hamilton RL; Wong JS; Luo J; Kennedy S; Davidson NO. 2006. Compensatory increase in hepatic lipogenesis in mice with conditional intestine-specific Mttp deficiency. J Biol Chem 281(7):4075-86. [PubMed: 16354657]  [MGI Ref ID J:108489]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryThis strain originated and is maintained as a homozygote on a B6;129S background.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. 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, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. 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, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


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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.
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