Prdm16lox/lox floxed mice may be useful for studying the role PRDM16 plays in the regulation of thermogenesis, obesity, and diabetes.
Bruce Spiegelman, Dana-Farber Cancer Institute
These Prdm16lox/lox mutant mice possess loxP sites flanking exon 9 of the PR domain containing 16 (Prdm16) gene. PRDM16 is a transcriptional regulator involved in the differentiation of brown and beige adipose tissue. Brown adipose tissue (BAT) is metabolically active because it contains an abundance of mitochondria and mitochondrial uncoupling protein 1 (UCP1), which utilize glucose and lipids to produce ATP. ATP production in BAT has a role in thermogenesis and has anti-obesity/diabetes effects. Beige fat refers to a type of UCP1 positive cells that emerge in white fat depots under certain conditions, and has also been found to be involved in thermogenesis. PRDM16 is also involved in craniofacial development. Homozygous Prdm16lox/lox mice are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 9 deleted in the cre-expressing tissues.
For Example, when bred to B6;FVB-Tg(Adipoq-cre)1Evdr/J transgenic mice (Stock No. 010803), expressing Cre recombinase in adipocytes, Prdm16-deficient mice have ablated beige adipocyte function in subcutaneous fat following cold exposure or β3-adrenergic agonist treatment, and also reduced energy expenditure following β3-adrenergic agonist treatment. They develop obesity on a high-fat diet, with severe insulin resistance and hepatic steatosis. They showed altered fat distribution with an increase in subcutaneous adipose tissue, and acquired properties of visceral fat, including decreased thermogenic and increased inflammatory gene expression and increased macrophage accumulation.
A targeting vector was designed to insert a loxP site upstream of exon 9 followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 9 of the PR domain containing 16 (Prdm16) gene. The construct was electroporated into 129Sv embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred to C57BL/6 mice. Offspring were bred with Rosa26-Flp transgenic mice to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. These Prdm16lox/lox mice were bred to C57BL/6J mice for at least 8 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1.1, Bruce M Spiegelman|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Prdm16, PR domain containing 16|
|Gene Synonym(s)||5730557K01Rik; 5730557K01Rik; CMD1LL; LVNC8; MEL1; Mel1; PFM13; RIKEN cDNA 5730557K01 gene; cleft secondary palate 1; csp1; csp1; line 27|
|Strain of Origin||129/Sv|
|Molecular Note||The targeting vector was designed to insert a loxP site upstream of exon 9 followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 9.|
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