These mice have a targeted mutation of the Nocturnin (Ccrn4l; CCR4 carbon catabolite repression 4-like (S. cerevisiae)) gene and may be useful in studying resistance to diet-induced obesity, physiologic rhythms downstream of the circadian clockwork, and post-transcriptional regulation of genes necessary for nutrient uptake, metabolism, and storage.
Joseph C Besharse, Medical College of Wisconsin
Mice homozygous for this Nocturnin (Ccrn4l or Noc) targeted mutation are viable and fertile, with no detectable Noc protein made from the targeted gene. Homozygotes are resistant to diet-induced obesity and remain lean on high-fat diets, with lower body weight and reduced visceral fat. Unlike lean lipodystrophic mouse models, Noc-deficient mice do not have fatty livers (hepatic steatosis) and do not exhibit increased activity or reduced food intake. In addition to changes in glucose tolerance and insulin sensitivity, homozygous mice may also have deficits in lipid metabolism or lipid uptake. Nocturnin-deficient mice may be useful in studying resistance to diet-induced obesity, physiologic rhythms downstream of the circadian clockwork, and post-transcriptional regulation of genes necessary for nutrient uptake, metabolism, and storage.
A targeting vector was designed to replace introns 2-3 and the coding region of exon 3 (which contains most of the protein coding sequence including the catalytic domain) of the targeted gene with a neomycin resistance cassette. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric males were bred with C57BL/6J females. Next, mutant mice were backcrossed to C57BL/6J inbred mice for at least 10 generations prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, J C Besharse|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Noct, nocturnin|
|Strain of Origin||129S2/SvPas|
|Molecular Note||The entire coding region of exon 3, which contains most of the protein coding sequence including the catalytic domain, was replaced with a neomycin resistance cassette. Absence of protein was confirmed in mutant liver homogenates.|
|Mutations Made By|| |
Joseph Besharse, Medical College of Wisconsin
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.129S2-Nocttm1Bjc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008841 in your Materials and Methods section.