Myh9flox mutant mice possess loxP sites flanking exon 1. Genome wide association studies associate single nucleotide polymorphisms (SNPs) in MYH9 with chronic kidney disease in African-Americans. These mice may be useful in generating conditional mutations to study hemostasis, glomerulosclerosis and kidney disease.
Myh9 (myosin, heavy chain 9, non-muscle) encodes a nonmuscle myosin IIA heavy chain involved in several functions including cytokinesis, cell motility and maintenance of cell shape. Genome wide association studies associate single nucleotide polymorphisms (SNPs) in MYH9 with chronic kidney disease in African-Americans. Myh9flox mutant mice possess loxP sites flanking exon 1. Homozygous mice are viable and fertile.
When Myh9flox mice are crossed with Pod::Cre mice the resulting offspring will have exon 1 deleted in kidney podocytes. Double mutant mice on the C57BL/6 background do not develop spontaneous proteinuria or renal insufficiency, however, when subjected to environmental stress via doxyrubicin hydrochloride (Adriamycin), Myh9 podocyte-deleted mice develop albuminuria, focal and segmental glomerulosclerosis, foot process fusion and foot process effacement. When crossed to mice with widespread Cre recombinase expression, deletion of Myh9 is lethal.
This strain is unpublished on the FVB background. The donating investigator indicates that FVB mice are more sensitive to glomerular disease than C57BL/6 mice
The Myh9tm1.1Gac targeting vector was designed to insert a loxP site upstream of exon 1 followed by a loxP-flanked neomycin resistance (neo) cassette downstream of exon 1 in the Myh9 gene. The construct was electroporated into 129/Sv-derived embryonic stem (ES) cells. Transient Cre expression in targeted cells excised the neo cassette leaving exon 1 flanked by loxP sites. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice for at least 5 generations. Mice were intercrossed with B6(SJL)-Tg(NPHS2-cre)295Lbh (Pod::Cre) and double mutant mice (Pod::Cre;Myh9f) were backcrossed to FVB/NJ mice by marker assisted selection (speed congenic) for 4 generations and then by traditional backcross for 10 generations. Upon arrival at the MMRRC, mice were selected for Myh9tm1.1Gac and established as a separate colony.
|Allele Name||targeted mutation 1.1, Christian Gachet|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||MYH9Flx; Myh9flox|
|Gene Symbol and Name||Myh9, myosin, heavy polypeptide 9, non-muscle|
|Strain of Origin||129|
|Molecular Note||A loxP site was inserted upstream of exon 1, and a floxed neo cassette was inserted downstream of exon 1. Transient expression in ES cells removed the neo cassette leaving exon 1 floxed.|
While maintaining a live colony, these mice are bred as heterozygous x FVB/NJ and reciprocal.
When using the MYH9Flx mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36749 in your Materials and Methods section.