This strain carries the Dusp6tm1Jmol knockout allele on a C57BL/6J-backcrossed background. Homozygotes demonstrate reduced adiposity, possibly due to reduced adipocyte differentiation. Body weight gain is attenuated on a high-fat diet and triglyceride contents are decreased in the liver.
Haiyan Xu, Rhode Island Hospital, Warren Alpert Medical School of Brown University
Dusp6 (dual specificity phosphatase 6; also called MKP3) is a negative regulator of extracellular signal-related kinase signaling. The gene plays an important role in obesity-related hyperglycemia by promoting hepatic glucose output.
This strain incorporates the Dusp6tm1Jmol allele (originally offered in Stock No. 009069) backcrossed further to C57BL/6J. In this allele, exons 1-3 of the gene are replaced by a neomycin cassette to create a knockout.
Homozygous deficiency attenuates body weight gain induced by a high-fat diet and protects mice from developing obesity-related hepatosteatosis. Triglyceride contents are dramatically decreased in the liver. Adiposity is reduced, possibly by repressing adipocyte differentiation. Animals exhibit increased energy expenditure, enhanced peripheral glucose disposal, and improved systemic insulin sensitivity.
Exons 1-3 were replaced with a neomycin resistance cassette via homologous recombination in a 129-derived embryonic stem cell line. Resultant chimeric animals were minimally backcrossed to C57BL/6 to create C57BL/6-129 mixed background Stock No. 009069. This strain was backcrossed to C57BL/6J for a further 9 generations by the donating laboratory.
|Allele Name||targeted mutation 1, Jeffery D Molkentin|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Dusp6, dual specificity phosphatase 6|
|Strain of Origin||129|
|Molecular Note||All 3 exons were replaced with a neo cassette via homologous recombination. Western blot analysis confirmed the absence of protein in the lung, spleen, thymus, and heart of homozygous mice.|
|Mutations Made By|| |
Jeffery Molkentin, Cincinnati Children's Hospital
Heterozygotes and homozygotes are viable and fertile.
When using the B6.129-Dusp6tm1Jmol/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #025564 in your Materials and Methods section.