Phenotypes associated with this allele

• Allele Symbol: Atp2a2^tm1.1Raco
• Allele Name: targeted mutation 1.1, Richard A Cohen
• Allele ID: MGI:5660869
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Atp2a2^tm1.1Raco/Atp2a2^tm1.1Raco	C57BL/6J-Atp2a2^tm1.1Raco/Raco	MGI:5780877
ht2	Atp2a2^tm1.1Raco/Atp2a2^+	C57BL/6J-Atp2a2^tm1.1Raco/Raco	MGI:5780878

Genotype
MGI:5780877

hm1

• Allelic Composition: Atp2a2^tm1.1Raco/Atp2a2^tm1.1Raco
• Genetic Background: C57BL/6J-Atp2a2^tm1.1Raco/Raco

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Lack of blood vessels and smaller size of E8.5 Atp2a2^tm1.1Raco/Atp2a2^tm1.1Raco (S674/S674) embryos

mortality/aging

embryonic lethality between somite formation and embryo turning, complete penetrance ( J:216004 )

• homozygotes are present up to E8.5, just prior to the initial period of vascular development, but not thereafter

embryo

decreased embryo size ( J:216004 )

• homozygotes are smaller than heterozygous embryos at E8.5

growth/size/body

decreased embryo size ( J:216004 )

• homozygotes are smaller than heterozygous embryos at E8.5

cardiovascular system

abnormal vascular development ( J:216004 )

• lack of blood vessels at E8.5

Genotype
MGI:5780878

ht2

• Allelic Composition: Atp2a2^tm1.1Raco/Atp2a2⁺
• Genetic Background: C57BL/6J-Atp2a2^tm1.1Raco/Raco

Impaired blood flow recovery at 21 and 28 days post hind limb ischemia in Atp2a2^tm1.1Raco/Atp2a2⁺ mice

cardiovascular system

abnormal physiological neovascularization ( J:216004 )

• impaired ischemic angiogenesis at 21 and 28 days after femoral artery ligation relative to wild-type controls

• significantly lower increase in SERCA S-glutathione adducts in the ischemic hind limb muscle at 3 days post femoral artery ligation relative to wild-type controls

decreased angiogenesis ( J:216004 )

• in a Matrigel assay, both basal and VEGF-induced capillary-like network formation are significantly impaired in cultured endothelial cells relative to wild-type cells

abnormal vascular endothelial cell migration ( J:216004 )

• impaired VEGF-mediated migration of microvascular endothelial cells in an in vitro monolayer scratch wound assay

• adenoviral overexpression of calreticulin, an ER Ca²⁺ binding protein, restores endothelial cell migration

abnormal blood circulation ( J:216004 )

• impaired blood flow recovery at 21 and 28 days post hind limb ischemia in adult (8- to 12-week-old) mice relative to wild-type controls

abnormal vascular endothelial cell physiology ( J:216004 )

• no significant increase in SERCA S-glutathione adducts in primary cardiac microvascular endothelial cells at 24 h after induction of hypoxia, unlike in wild-type endothelial cells

• decreased nitric oxide-induced (thapsigargin-sensitive) ⁴⁵Ca²⁺ uptake into the endoplasmic reticulum (ER) in cultured endothelial cells relative to wild-type cells

• in a Matrigel assay, both basal and vascular endothelial growth factor (VEGF)-induced capillary-like network formation are significantly impaired in cultured endothelial cells relative to wild-type cells

homeostasis/metabolism

abnormal calcium ion homeostasis ( J:216004 )

• decreased nitric oxide-induced ⁴⁵Ca²⁺ uptake into the ER in cultured cardiac microvascular endothelial cells relative to wild-type cells

• Fura-2 studies revealed decreased Ca²⁺ stores and decreased VEGF- and nitric oxide-induced Ca²⁺ influx

• adenoviral overexpression of calreticulin, an ER Ca²⁺ binding protein, increases ionomycin-releasable stores and VEGF-induced Ca²⁺ influx

cellular

abnormal vascular endothelial cell migration ( J:216004 )

• impaired VEGF-mediated migration of microvascular endothelial cells in an in vitro monolayer scratch wound assay

• adenoviral overexpression of calreticulin, an ER Ca²⁺ binding protein, restores endothelial cell migration