Description

Strain Information

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   27-MAY-09 Species laboratory mouse Generation N9+N1F3N1F5 (08-JUL-11) Generation Definitions   Donating Investigator Lawrence Chan,   Baylor College of Medicine

Description
Homozygous mice are viable and fertile, with absence of targeted allele expression confirmed in adipose tissue (mRNA) and plasma (adiponectin protein). While homozygous mice have normal glucose tolerance and insulin resistance, beta-oxidation activity is significantly increased in muscle and liver. Homozygotes also have endothelial dysfunction (increased leukocyte rolling and leukocyte adhesion), are protected from DSS-induced colitis, and are more susceptible to myocardial ischemia/reperfusion. When fed a high fat diet, obese homozygotes are significantly heavier with increased insulin levels and altered insulin resistance. These adiponectin-deficient (Adipoq^-/- or Adipo^-/-) mice may be useful in studying obesity, diabetes, insulin resistance, metabolism, inflammation, leukocyte-endothelium interactions, and colitis.

Development
A targeting vector was designed to replace exon 2 of the targeted gene with a PGKneo cassette. This construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and chimeric mice were bred with C57BL/6J to generate mutant mice. Next, mutant mice were backcrossed to C57BL/6J for at least eight generations prior to sending to The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6J inbred mice for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. This revealed 2 markers on chromosome 15 (~57.0 Mbp and ~88.2 Mbp) that were not fixed for C57BL/6 allele-type (e.g.: segregating or fixed for 129 allele-type markers). This may represent a large region of chromosome 15 that is segregating or fixed as homozygous for 129 allele-type.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Adipoq

010803

B6;FVB-Tg(Adipoq-cre)1Evdr/J

View Strains carrying other alleles of Adipoq     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Adipoq^tm1Chan/Adipoq⁺

        B6.129-Adipoq^tm1Chan

• immune system phenotype
• abnormal leukocyte physiology
  • leukocyte rolling velocity is decreased compared to in wild type mice   (MGI Ref ID J:122020)
  • leukocyte adhesion to vascular endothelium is increased 2.5-fold compared in wild-type cells   (MGI Ref ID J:122020)
  • however, leukocyte physiology is normalized by treatment with human recombinant adiponectin   (MGI Ref ID J:122020)
• increased leukocyte cell number
  • mice exhibit an increase in rolling leukocytes in peri-intestinal venules compared to in wild-type mice that is not as great as in homozygotes   (MGI Ref ID J:122020)
  • however, total leukocyte counts are normal   (MGI Ref ID J:122020)
• cardiovascular system phenotype
• abnormal vascular endothelial cell physiology
  • ex vivo, adhesion of aortic endothelium to formyl-Met-Leu-Phe-activated human monocytic cells is increased compared to wild-type endothelium   (MGI Ref ID J:122020)
• homeostasis/metabolism phenotype
• decreased adiponectin level
  • adiponectin levels are decreased 58% compared to in wild-type mice   (MGI Ref ID J:122020)
• hematopoietic system phenotype
• increased leukocyte cell number
  • mice exhibit an increase in rolling leukocytes in peri-intestinal venules compared to in wild-type mice that is not as great as in homozygotes   (MGI Ref ID J:122020)
  • however, total leukocyte counts are normal   (MGI Ref ID J:122020)

Adipoq^tm1Chan/Adipoq^tm1Chan

        B6.129-Adipoq^tm1Chan

• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype
  • mice exhibit normal glucose homeostasis and response to a high fat diet   (MGI Ref ID J:79122)
• • abnormal lipid homeostasis
    • beta oxidization is decreased 47% in muscle cells and 30% in hepatocytes compared to in wild-type mice   (MGI Ref ID J:79122)
  • abnormal nitric oxide homeostasis
    • nitric oxide production is decreased 40% compared to in wild-type mice   (MGI Ref ID J:122020)
    • however, treatment with human recombinant adiponectin restores nitric oxide levels to near normal   (MGI Ref ID J:122020)
  • decreased adiponectin level
    • adiponectin is virtually undetectable in the plasma unlike in wild-type mice   (MGI Ref ID J:122020)
• immune system phenotype
• abnormal leukocyte physiology
  • leukocyte rolling velocity is decreased compared to in heterozygous and wild type mice   (MGI Ref ID J:122020)
  • leukocyte adhesion to vascular endothelium is increased 5-fold compared in wild-type cells   (MGI Ref ID J:122020)
  • however, leukocyte physiology is normalized by treatment with human recombinant adiponectin   (MGI Ref ID J:122020)
• increased leukocyte cell number
  • mice exhibit a 2-fold increase in rolling leukocytes in peri-intestinal venules compared to in wild-type mice   (MGI Ref ID J:122020)
  • however, total leukocyte counts are normal   (MGI Ref ID J:122020)
• cardiovascular system phenotype
• abnormal vascular endothelial cell physiology
  • ex vivo, adhesion of aortic endothelium to formyl-Met-Leu-Phe-activated human monocytic cells is increased compared to heterozygous and wild-type endothelium   (MGI Ref ID J:122020)
• hematopoietic system phenotype
• increased leukocyte cell number
  • mice exhibit a 2-fold increase in rolling leukocytes in peri-intestinal venules compared to in wild-type mice   (MGI Ref ID J:122020)
  • however, total leukocyte counts are normal   (MGI Ref ID J:122020)

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

Adipoq^tm1Chan/Adipoq^tm1Chan

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• renal/urinary system phenotype
• albuminuria
  • mice exhibit a 2-fold increase in urine albumin levels compared to in wild-type mice between 1 and 3 months that increased further at 4 months of age   (MGI Ref ID J:136297)
  • within 2 months, stereptozotocin-induced diabetic mice exhibit a greater increase in urine albumin levels than in similarly treated wild-type mice that progressively increases at 4 months after diabetes induction   (MGI Ref ID J:136297)
  • however, treatment with adiponectin restores normoalbuminuria   (MGI Ref ID J:136297)
• fused podocyte foot processes
  • at 3 months   (MGI Ref ID J:136297)
• cellular phenotype
• oxidative stress
  • mice exhibit an increase in urine hydrogen peroxide levels compared to in wild-type mice   (MGI Ref ID J:136297)
  • stereptozotocin-induced diabetic mice exhibit a greater increase in urine hydrogen peroxide levels than in similarly treated wild-type mice   (MGI Ref ID J:136297)
  • however, urine hydrogen peroxide levels are normalize by treatment with adiponectin   (MGI Ref ID J:136297)
• homeostasis/metabolism phenotype
• albuminuria
  • mice exhibit a 2-fold increase in urine albumin levels compared to in wild-type mice between 1 and 3 months that increased further at 4 months of age   (MGI Ref ID J:136297)
  • within 2 months, stereptozotocin-induced diabetic mice exhibit a greater increase in urine albumin levels than in similarly treated wild-type mice that progressively increases at 4 months after diabetes induction   (MGI Ref ID J:136297)
  • however, treatment with adiponectin restores normoalbuminuria   (MGI Ref ID J:136297)

Adipoq^tm1Chan/Adipoq^tm1Chan

        involves: 129S1/Sv * 129X1/SvJ

• growth/size phenotype
• increased body weight
  • after 22 weeks   (MGI Ref ID J:138678)
• homeostasis/metabolism phenotype
• abnormal lipid homeostasis
  • beta-oxidization in skeletal muscles is increased compared to in wild-type mice   (MGI Ref ID J:138678)
• muscle phenotype
• abnormal skeletal muscle fiber morphology
  • in the tibialis, IIB muscle fiber area is increased compared to in wild-type muscle   (MGI Ref ID J:138678)

View Research Applications

Research Applications

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

Cardiovascular Research
Ischemia studies
Vascular Defects
      defective leukocyte function

Diabetes and Obesity Research
Insulin Resistance
      diet-induced
Obesity With Diabetes
      diet-induced
Obesity Without Diabetes
      diet-induced
Type 2 Diabetes (NIDDM)
      diet-induced

Immunology and Inflammation Research
Autoimmunity
Immunodeficiency
      Inflammatory bowel disease
Inflammation
      Inflammatory bowel disease

Internal/Organ Research
Gastrointestinal Defects
      colitis
Wound Healing

Metabolism Research
Free Radical Research

Research Tools
Cardiovascular Research
Diabetes and Obesity Research
Immunology and Inflammation Research
Internal/Organ Research
Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Adipoqtm1Chan
Allele Name		targeted mutation 1, Lawrence Chan
Allele Type		Targeted (knock-out)
Common Name(s)		ADN-; Ad-; Adipo-;
Mutation Made By		Lawrence Chan,   Baylor College of Medicine
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Adipoq, adiponectin, C1Q and collagen domain containing
Chromosome		16
Gene Common Name(s)		ACDC; ACRP30; ADIPQTL1; ADPN; APM-1; APM1; APN; Acdc; Acrp30; GBP28; adipo; adipocyte complement related protein; adipocyte, C1Q and collagen domain containing; adiponectin;
Molecular Note		Exon 2 was replaced by a floxed neo cassette inserted by homologous recombination. Transcript was undetected in adipose tissue by Northern blot analysis of homozygous mutant mice. The lack of immunoreactivity by Western blot analysis using a carboxy terminal antibody indicated an absence of normal and truncated protein. [MGI Ref ID J:79122]

Genotyping

Genotyping Information

Genotyping Protocols

Adipoq^tm1Chan, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Fayad R; Pini M; Sennello JA; Cabay RJ; Chan L; Xu A; Fantuzzi G. 2007. Adiponectin deficiency protects mice from chemically induced colonic inflammation. Gastroenterology 132(2):601-14. [PubMed: 17258715]  [MGI Ref ID J:128222]

Ma K; Cabrero A; Saha PK; Kojima H; Li L; Chang BH; Paul A; Chan L. 2002. Increased beta -oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin. J Biol Chem 277(38):34658-61. [PubMed: 12151381]  [MGI Ref ID J:79122]

Ouedraogo R; Gong Y; Berzins B; Wu X; Mahadev K; Hough K; Chan L; Goldstein BJ; Scalia R. 2007. Adiponectin deficiency increases leukocyte-endothelium interactions via upregulation of endothelial cell adhesion molecules in vivo. J Clin Invest 117(6):1718-26. [PubMed: 17549259]  [MGI Ref ID J:122020]

Tao L; Gao E; Jiao X; Yuan Y; Li S; Christopher TA; Lopez BL; Koch W; Chan L; Goldstein BJ; Ma XL. 2007. Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation 115(11):1408-16. [PubMed: 17339545]  [MGI Ref ID J:133046]

Wu H; Ghosh S; Perrard XD; Feng L; Garcia GE; Perrard JL; Sweeney JF; Peterson LE; Chan L; Smith CW; Ballantyne CM. 2007. T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation 115(8):1029-38. [PubMed: 17296858]  [MGI Ref ID J:132316]

Additional References

Adipoq^tm1Chan related

Agrawal-Singh S; Koschmieder S; Gelsing S; Stocking C; Stehling M; Thiede C; Thoennissen NH; Kohler G; Valk PJ; Delwel R; Mills K; Baumer N; Tickenbrock L; Hansen K; Berdel WE; Muller-Tidow C; Serve H. 2010. Pim2 cooperates with PML-RARalpha to induce acute myeloid leukemia in a bone marrow transplantation model. Blood 115(22):4507-16. [PubMed: 20215640]  [MGI Ref ID J:161561]

Chang J; Li Y; Huang Y; Lam KS; Hoo RL; Wong WT; Cheng KK; Wang Y; Vanhoutte PM; Xu A. 2010. Adiponectin prevents diabetic premature senescence of endothelial progenitor cells and promotes endothelial repair by suppressing the p38 MAP kinase/p16INK4A signaling pathway. Diabetes 59(11):2949-59. [PubMed: 20802255]  [MGI Ref ID J:169726]

Krause MP; Liu Y; Vu V; Chan L; Xu A; Riddell MC; Sweeney G; Hawke TJ. 2008. Adiponectin is expressed by skeletal muscle fibers and influences muscle phenotype and function. Am J Physiol Cell Physiol 295(1):C203-12. [PubMed: 18463233]  [MGI Ref ID J:138678]

Lam JB; Chow KH; Xu A; Lam KS; Liu J; Wong NS; Moon RT; Shepherd PR; Cooper GJ; Wang Y. 2009. Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities. PLoS ONE 4(3):e4968. [PubMed: 19319191]  [MGI Ref ID J:147458]

Lee EB; Warmann G; Dhir R; Ahima RS. 2011. Metabolic dysfunction associated with adiponectin deficiency enhances kainic Acid-induced seizure severity. J Neurosci 31(40):14361-6. [PubMed: 21976521]  [MGI Ref ID J:177436]

Lee S; Park Y; Dellsperger KC; Zhang C. 2011. Exercise training improves endothelial function via adiponectin-dependent and independent pathways in type 2 diabetic mice. Am J Physiol Heart Circ Physiol :. [PubMed: 21602470]  [MGI Ref ID J:173343]

Lovren F; Pan Y; Quan A; Szmitko PE; Singh KK; Shukla PC; Gupta M; Chan L; Al-Omran M; Teoh H; Verma S. 2010. Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages. Am J Physiol Heart Circ Physiol 299(3):H656-63. [PubMed: 20622108]  [MGI Ref ID J:164606]

Pini M; Gove ME; Fayad R; Cabay RJ; Fantuzzi G. 2009. Adiponectin deficiency does not affect development and progression of spontaneous colitis in IL-10 knockout mice. Am J Physiol Gastrointest Liver Physiol 296(2):G382-7. [PubMed: 19074637]  [MGI Ref ID J:146374]

Pini M; Sennello JA; Chan L; Fantuzzi G. 2006. Adiponectin deficiency does not affect the inflammatory response to endotoxin or concanavalin a in mice. Endocrinology 147(11):5019-22. [PubMed: 16901963]  [MGI Ref ID J:129728]

Ponemone V; Fayad R; Gove ME; Pini M; Fantuzzi G. 2010. Effect of adiponectin deficiency on intestinal damage and hematopoietic responses of mice exposed to gamma radiation. Mutat Res 690(1-2):102-107. [PubMed: 19583972]  [MGI Ref ID J:162602]

Sharma K; Ramachandrarao S; Qiu G; Usui HK; Zhu Y; Dunn SR; Ouedraogo R; Hough K; McCue P; Chan L; Falkner B; Goldstein BJ. 2008. Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest 118(5):1645-56. [PubMed: 18431508]  [MGI Ref ID J:136297]

Tao L; Wang Y; Gao E; Zhang H; Yuan Y; Lau WB; Chan L; Koch WJ; Ma XL. 2010. Adiponectin: an indispensable molecule in rosiglitazone cardioprotection following myocardial infarction. Circ Res 106(2):409-17. [PubMed: 19940263]  [MGI Ref ID J:170058]

Teoh H; Quan A; Bang KW; Wang G; Lovren F; Vu V; Haitsma JJ; Szmitko PE; Al-Omran M; Wang CH; Gupta M; Peterson MD; Zhang H; Chan L; Freedman J; Sweeney G; Verma S. 2008. Adiponectin deficiency promotes endothelial activation and profoundly exacerbates sepsis-related mortality. Am J Physiol Endocrinol Metab 295(3):E658-64. [PubMed: 18628355]  [MGI Ref ID J:139977]

Tu Q; Zhang J; Dong LQ; Saunders E; Luo E; Tang J; Chen J. 2011. Adiponectin Inhibits Osteoclastogenesis and Bone Resorption via APPL1-mediated Suppression of Akt1. J Biol Chem 286(14):12542-53. [PubMed: 21300805]  [MGI Ref ID J:171143]

Wilk S; Scheibenbogen C; Bauer S; Jenke A; Rother M; Guerreiro M; Kudernatsch R; Goerner N; Poller W; Elligsen-Merkel D; Utku N; Magrane J; Volk HD; Skurk C. 2011. Adiponectin is a negative regulator of antigen-activated T cells. Eur J Immunol 41(8):2323-32. [PubMed: 21538348]  [MGI Ref ID J:177295]

Wong WT; Tian XY; Xu A; Yu J; Lau CW; Hoo RL; Wang Y; Lee VW; Lam KS; Vanhoutte PM; Huang Y. 2011. Adiponectin is required for PPARgamma-mediated improvement of endothelial function in diabetic mice. Cell Metab 14(1):104-15. [PubMed: 21723508]  [MGI Ref ID J:176078]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred.
Mating System	Homozygote x Homozygote         (Female x Male)   27-MAY-09
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

See Terms of Use tab for General Terms and Conditions

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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