These mice carry a knock-out mutation of Mir22 (microRNA 22) and exhibit impaired cardiac intracellular calcium homeostasis and increased sensitivity to hemodynamic stress.
Antony Rodriguez, Baylor College of Medicine
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for these C57BL/6J-congenic miR-22- mice. It should be noted that the phenotype of these mice could vary from that originally described on a 129S genetic background (129S.miR-22-; Stock No. 018155). We may modify the C57BL/6J-congenic miR-22- strain description if necessary as published results become available.
The phenotype for 129S.miR-22- animals is:
Mir22 (microRNA 22) expresson is frequently dysregulated in diseased human hearts. Mice that are homozygous for the knock-out mutation of Mir22 (miR-22-/-) are viable and fertile, but are not produced at expected numbers from heterozygous crosses. Null mice produce small litters of 2 to 3 pups. No gene product (mRNA) is detected by qPCR analysis of heart tissue. Although no evidence of cardiac pathology is evident under basal conditions, homozygous mice are impaired in contractile reserve to dobutamine and intracellular calcium homeostasis. Homozygotes exhibit increased sensitivity to heart failure after transverse aortic constriction (TAC), as evidenced by loss of contractility, ventricular dilatation, and increased fibrosis.
A targeting vector containing a loxP flanked PGK-EM7-NeobpA cassette was used to disrupt Mir22 (microRNA 22).
The donating investigator reported the construct was electroporated into AB2.2 embryonic stem (ES) cells (which MGI attributes to 129S7/SvEvBrd). Correctly targeted ES cells were injected into recipient blastocysts. The resulting male chimeric animals were crossed to 129S5/SvEvBrd female mice. For germline removal of the floxed selection cassette, the mice were crossed to CMV-cre mice on a 129S5/SvEvBrd background. In 2012, 129S.miR-22- male mice were sent to The Jackson Laboratory Repository. The mice were then bred to 129S1/SvImJ inbred females (Stock No. 002448) at least once to establish Stock No. 018155.
In 2015, some miR-22- mice were backcrossed to C57BL/6J inbred mice (Stock No. 000664) for many generations using a marker-assisted, speed congenic approach to generate this C57BL/6J-congenic miR-22- colony (Stock No. 027792). As of December 2016, the colony is N3 (~90.5-94.9% C57BL/6J), with additional backcross generations in progress.
|Allele Name||targeted mutation 1.1, Antony Rodriguez|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Mir22, microRNA 22|
|Strain of Origin||129S7/SvEvBrd-Hprtb-m2|
|Molecular Note||A targeting vector containing a loxP flanked PGK-EM7-NeobpA cassette was used to disrupt Mir22 (microRNA 22). Cre-mediated recombination removed the neo cassette. No gene product (mRNA) is detected by qPCR analysis of heart tissue.|
Mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for several generations using a marker-assisted, speed congenic approach to establish this congenic strain. When maintaining the live congenic colony, heterozygous mice may be bred together, to wildtype mice from the colony, or to C57BL/6J inbred mice.
Of note, on a 129S genetic background, mice that are homozygous for the knock-out mutation of Mir22 (miR-22-/-) are viable and fertile, but are not produced at expected numbers from heterozygous crosses. Null mice produce small litters of 2 to 3 pups.
When using the miR-22- (C57BL/6J) mouse strain in a publication, please cite the originating article(s) and include JAX stock #027992 in your Materials and Methods section.