B6;129-Adipoq^tm1Chan/J

Stock number: 008195
Product name: Adipo^-
Research areas: Cardiovascular Research, Dermatology Research, Developmental Biology Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

Adipoq^tm1Chan homozygotes exhibit endothelial dysfunction and are more susceptible to myocardial ischemia/reperfusion. These mice may be useful in studying obesity, diabetes, insulin resistance, metabolism, inflammation, leukocyte-endothelium interactions, and colitis.

Detailed 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.

At The Jackson Laboratory, it is our experience that breeding Adipoq^tm1Chan homozygous mice together frequently results in pups with significant hair loss by wean age (3 weeks). It is not determined if this phenotype is caused by the genotype of the pups, or if the phenotype is imparted upon the pups due to the genotype of the lactating/nursing female. In most cases, the hair loss phenotype is reversed after weaning, with some pups growing a full coat by 6 weeks of age.

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. The donating investigator reported that mutant mice were backcrossed to C57BL/6J (see SNP note below) 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 and one marker on Chromosome 19 that are segregating for 129 suggesting an incomplete backcross.

Allele

Symbol: Adipoq^tm1Chan
Name: targeted mutation 1, Lawrence Chan
MGI accession ID: MGI:2388007
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Ad^-; Adipo^-; ADN^-
Marker symbol: Adipoq
Marker name: adiponectin, C1Q and collagen domain containing
Marker synonyms: Acdc; ACRP30; Ad; Adid; adipo; adiponectin; ADIPQTL1; ADPN; APM1; APM-1; APN; GBP28
Chromosome: 16
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
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.