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
Mir22 (microRNA 22) expresson is frequently dysregulated in diseased human hearts. Mice that are homozygous for this targeted mutation of Mir22 are viable, 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. Upon arrival at The Jackson Laboratory, the mice were crossed to 129S1/SvImJ (Stock No. 002448) at least once to establish the colony.
|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.|
Mice that are homozygous for this targeted mutation of Mir22 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 maintaining a live colony, heterozygous mice may be bred together.
When using the miR-22- (129) mouse strain in a publication, please cite the originating article(s) and include JAX stock #018155 in your Materials and Methods section.