These Id2 knockout mice exhibit reduced body weight, a high degree of homozygous lethality, disrupted circadian rhythms, altered locomotor and feeding patterns and enhanced insulin sensitivity and glucose uptake (males). This strain may be useful for studying ID2 as a regulator of circadian rhythm and metabolic homeostasis.
Giles Duffield, University of Notre Dame
ID2 (inhibitor of DNA binding 2) is a transcriptional regulator containing a helix-loop-helix domain. ID genes are involved in multiple systems including circadian rhythm biology, glucose and lipid metabolism, immune cell function, organ development and tumorigenesis. The Id2 knockout allele has a PGK-neo cassette replacing exons 1-2 of the gene.
Mice homozygous for this null allele exhibit multiple alterations in the circadian system including: disrupted circadian rhythms (25% of mice), rapid entrainment following alterations in photoschedule and an increase in light-induced phase shifts. Some mice demonstrate circling behavior and jumpiness, although overall locomotor activity is reduced. Males exhibit increased glucose tolerance, increased glucose uptake in skeletal muscle and improved insulin sensitivity.
Males are smaller than littermates, and lean, although they consume more food than females. Females are also smaller, but the difference is less pronounced.
Adipogenesis is impaired, resulting in reduced fat deposits and lipid storage in white adipose tissue and liver, respectively.
The donating investigator reports that on the C57BL/6 background few homozygotes survive (less than 1%). The strain is maintained on a mixed 129X1, C57BL/6, FVB/N background, on this background homozygous survivorship is increased to 10%. Survivorship is increased under germ-free conditions, suggesting that mice are immunocompromised. This strain may be useful for studying ID2 as a regulator of circadian rhythm and metabolic homeostasis.
A targeting vector containing the neomycin resistance cassette was used to replace a region 560 bp 5’ upstream of the transcription start site and exons 1 and 2 using homologous recombination. Exons 1-2 encode the entire coding domain. The construct was electroporated into 129X1/SvJ-derived JM-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice and then crossed to FVB/N mice. The donating investigator maintains the strain on a mixed 129X1/C57BL/6/FVB background. Upon arrival at The Jackson Laboratory, mice were bred to FVB/NJ for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Mark A Israel|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Id2, inhibitor of DNA binding 2|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A targeting vector containing the neomycin resistance cassette was used to replace a region 560 bp 5' upstream of the transcription start site and exons 1 and 2 using homologous recombination. Exons 1-2 encode the entire coding domain. Western blot and immunoprecipitation of xx tissues confirmed that no protein was expressed in mutant mice. Western blot analysis of liver tissues confirmed that no protein was expressed in mutant mice.|
While maintaining a live colony, these mice are bred as heterozygotes. Few homozygotes survive the early postnatal period and surviving females are unable to nurture pups.
When using the Id2- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #41568 in your Materials and Methods section.