These ATPase, Ca++ transporting (Atp2a3 or Serca3) knockout mice exhibit reduced acetylecholine (Ach)-induced aortic relaxation and diminished Ach-responsive Ca2+ stores. These mice may be useful for studying endothelial Ca2+ signaling and aortic smooth muscle relaxation/contraction.
Gary E Shull, University of Cincinnati
Homozygotes: A targeting vector was designed to insert a neomycin resistance (neo) cassette into exon 5 of the ATPase, Ca++ transporting, ubiquitous (Atp2a3 or Serca3) gene, abolishing gene function. Serca3 is a Sarco(endo)plasmic reticulum Ca2+ ATPase which is expressed in endothelial cells, in epithelial cells of trachea, intestine, and
salivary glands, and in platelets, mast cells, and lymphocytes. In these mice, acetylecholine (Ach)-induced aortic relaxation is reduced, and Ach-responsive Ca2+ stores, along with intracellular Ca2+ signaling, are diminished. These Serca3-/-mice do, however, exhibit normal basal blood pressure, glucose tolerance, and insulin secretion. These mice may be useful for studying endothelial Ca2+ signaling and aortic smooth muscle relaxation/contraction.
Heterozygote: Heterozygous mice are viable, fertile, and normal in size. They exhibit normal growth, and are phenotypically similar to wildtype mice
A targeting vector was designed to insert a neomycin resistance (neo) cassette into exon 5 of the ATPase, Ca++ transporting, ubiquitous (Atp2a3 or Serca3) gene. The construct was electroporated into 129-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. The resulting chimeric males were bred to Black Swiss females, and these mice were subsequently backcrossed to FVB/N mice for at least 10 generations. Upon arrival at The Jackson Laboratory, mice were bred to FVB/NJ inbred mice for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Gary E Shull|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Atp2a3, ATPase, Ca++ transporting, ubiquitous|
|Strain of Origin||Not Specified|
|Molecular Note||A neomycin resistance gene was inserted into exon 5, which encodes amino acids 109 through 154. Northern blot analysis of RNA isolated from colon, lung, and aorta tissue showed the presence of a shortened transcript in homozygous mutant mice. Sequence analysis of the mutant message identified a cryptic donor site in exon 5 that led to the excision of 84 nucleotides encoding amino acids 127 through 154. Transfection of microsomes, showed that the mutant protein product was incapable of calcium-uptake.|
|Mutations Made By|| |
Gary Shull, University of Cincinnati
When maintaining a live colony, homozygous mice may be bred together.
When using the FVB.Cg-Atp2a3tm1Ges/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34260 in your Materials and Methods section.