Mice homozygous for a null Atp2b4 or PMCA4 (Ca++ transporting ATPase, plasma membrane 4) allele exhibit male infertility (due to loss of hyperactivate sperm motility), increased apoptosis in portal vein smooth muscle cells, accelerated osteoclastogenesis, osteopenia, attenuated Ca signaling in B lymphocytes,and increased cardiac hypertrophy following pressure overload stimulation. This strain may be useful for studying calcium signaling in male infertility, lymphocytes, osteoclasts and smooth muscle contractility.
Gary E Shull, University of Cincinnati
A targeting vector containing the neomycin resistance gene was used to replace codons 448-474 in exon 11, a region encoding the catalytic phosphorylation site. The construct was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to Black Swiss mice. Mice from the colony were then backcrossed to FVB/N for at least 10 generations. Upon arrival, mice were bred to FVB/NJ for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Gary E Shull|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Atp2b4, ATPase, Ca++ transporting, plasma membrane 4|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A region of exon 11 encoding amino acids 448-474, including the catalytic phosphorylation site (aspartic acid 465), was replaced with a neomycin resistance gene. Northern blot showed no reduction in mRNA levels in mutant mice. Exon-11-deficient mice express a mutant PMCA4 mRNA as a consequence of exon-10 splicing to exon-12, which preserves the reading frame and enables these mice to produce functionless mutant PMCA4a and PMCA4b proteins (devoid of a catalytic site).|
While maintaining a live colony, these mice are bred as heterozygotes or homozygous female x heterozygous male. Male mice homozygous for the mutation are infertile.
When using the FVB.129(Cg)-Atp2b4tm1Ges/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36807 in your Materials and Methods section.