Phenotypes associated with this allele

• Allele Symbol: Slc8a1^tm1Yin
• Allele Name: targeted mutation 1, Yo-ichi Nabeshima
• Allele ID: MGI:2384549
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slc8a1^tm1Yin/Slc8a1^tm1Yin	involves: 129X1/SvJ * C57BL/6J	MGI:3622336
ht2	Slc8a1^tm1Yin/Slc8a1^+	involves: 129X1/SvJ * C57BL/6J	MGI:3622337

Genotype
MGI:3622336

hm1

• Allelic Composition: Slc8a1^tm1Yin/Slc8a1^tm1Yin
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

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

Slc8a1^tm1Yin/Slc8a1^tm1Yin embryos lack identifiable vitelline blood vessels

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:65985 )

• homozygotes die between E9.0 and E10.0

cardiovascular system

abnormal vitelline vasculature morphology ( J:65985 )

• at E9.5, homozygotes exhibit normal blood islands, indicating normal embryonic hematopoiesis; however, mutant capillaries appear dilated

absent vitelline blood vessels ( J:65985 )

• at E9.5, homozygotes lack identifiable vitelline blood vessels

decreased myocardial fiber number ( J:65985 )

• at E9.5, mutant hearts contain significantly fewer ventricular cardiomyocytes, with some cells exhibiting nuclear condensation and cell shrinkage

abnormal fetal cardiomyocyte morphology ( J:65985 , J:102564 )

• at E9.5, mutant hearts contain significantly fewer ventricular cardiomyocytes, with some cells exhibiting nuclear condensation and cell shrinkage (J:65985)

• at E9.5, homozygotes show severe disorganization of cardiac myofibrils, with swollen mitochondria and myofilaments distributed at random or aligned with Z-lines (J:102564)

thin ventricular wall ( J:65985 )

• at E9.5, homozygotes display a very thin ventricular wall

enlarged pericardium ( J:65985 )

• at E9.5, homozygotes exhibit enlarged pericardial sacs

abnormal cardiovascular system physiology ( J:65985 )

• at E9.5, mutant hearts fail to show fast Ca²⁺ transients and do not respond to either removal or reapplication of Na⁺, indicating loss of reverse mode of Na⁺/Ca²⁺ exchange activity

• in addition, mutant hearts exhibit a delay in the decay phase of caffeine-induced Ca2⁺ transients; the decay phase is not affected by the presence of Na⁺, indicating loss of the forward mode Na⁺/Ca²⁺ exchange activity

poor circulation ( J:65985 )

• at E9.5, homozygotes display absence of erythrocyte circulation in the yolk sacs, placental labyrinth, and chorionic plate as a result of heartbeat deficiency

absent heartbeat ( J:65985 )

• at E9.5, ~70% of mutant embryos fail to exhibit spontaneous rhythmic contractions (no heartbeats)

irregular heartbeat ( J:65985 )

• at E9.5, ~30% of mutant embryos exhibit very slow and arrhythmic contractions

increased cardiomyocyte apoptosis ( J:65985 )

• at E9.5, homozygotes exhibit a significant number of TUNEL-positive apoptotic cardiomyocytes

• apoptosis of neuroepithelial cells is also observed in the neural tube, possibly secondary to ischemia caused by absence of blood circulation

embryo

abnormal vitelline vasculature morphology ( J:65985 )

• at E9.5, homozygotes exhibit normal blood islands, indicating normal embryonic hematopoiesis; however, mutant capillaries appear dilated

absent vitelline blood vessels ( J:65985 )

• at E9.5, homozygotes lack identifiable vitelline blood vessels

decreased embryo size ( J:65985 )

• at E9.5, homozygotes are smaller than wild-type embryos; however, mutant limb buds, cranial neural tube, and somites appear unaffected

abnormal vitelline vascular remodeling ( J:65985 )

• at E9.5, mutant yolk sacs exhibit a honeycomb-like vasculature but lack branching vitelline vessels and have an enlarged capillary plexus

growth/size/body

decreased embryo size ( J:65985 )

• at E9.5, homozygotes are smaller than wild-type embryos; however, mutant limb buds, cranial neural tube, and somites appear unaffected

muscle

decreased myocardial fiber number ( J:65985 )

• at E9.5, mutant hearts contain significantly fewer ventricular cardiomyocytes, with some cells exhibiting nuclear condensation and cell shrinkage

increased cardiomyocyte apoptosis ( J:65985 )

• at E9.5, homozygotes exhibit a significant number of TUNEL-positive apoptotic cardiomyocytes

• apoptosis of neuroepithelial cells is also observed in the neural tube, possibly secondary to ischemia caused by absence of blood circulation

absent Z line ( J:102564 )

• at E9.5, mutant cardiomyocytes show reduced myofilament bundles that form no or single Z-lines; intercalated-disk-like structures are associated with myofilament bundles which have no Z-lines

cellular

increased cardiomyocyte apoptosis ( J:65985 )

• at E9.5, homozygotes exhibit a significant number of TUNEL-positive apoptotic cardiomyocytes

• apoptosis of neuroepithelial cells is also observed in the neural tube, possibly secondary to ischemia caused by absence of blood circulation

abnormal mitochondrial crista morphology ( J:102564 )

• at E9.5, mutant cardiomyocytes exhibit dilated cristae

abnormal mitochondrial matrix morphology ( J:102564 )

• at E9.5, mutant cardiomyocytes exhibit low electron-dense matrix

abnormal mitochondrial shape ( J:102564 )

• at E9.5, mutant cardiomyocytes exhibit swollen mitochondria of irregular shape

dilated mitochondrion ( J:102564 )

• at E9.5, mutant cardiomyocytes exhibit swollen mitochondria of irregular shape

Genotype
MGI:3622337

ht2

• Allelic Composition: Slc8a1^tm1Yin/Slc8a1⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

cardiovascular system

heart left ventricle hypertrophy ( J:75050 )

• heterozygotes exhibit no significant differences in cardiac morphology e.g. interventricular septal wall thickness, LV posterior wall thickness, LV end-diastolic dimension, or LV end-systolic dimension relative to wild-type mice

• however, at 3 wks after transverse aorta constriction (""pressure overload""), heterozygotes show a higher increase in left ventricular weight to body weight ratio and in LV wall thickness than wild-type mice

cardiac interstitial fibrosis ( J:75050 )

• at 3 wks after transverse aorta constriction (""pressure overload""), heterozygous hearts show significantly increased interstitial collagen accumulation relative to wild-type hearts

abnormal cardiovascular system physiology ( J:65985 )

• adult heterozygotes display a ~50% reduction of Na⁺-dependent Ca²⁺ exchange activity in aortic smooth muscles

increased ventricle muscle contractility ( J:75050 )

• heterozygotes exhibit normal baseline cardiac functions with no significant differences in systolic left ventricular pressure (LVP), end-diastolic pressure (EDP), and positive and negative first derivatives of left ventricular pressure (dP/dt, -dP/dt) relative to wild-type mice

• however, at 3 wks after transverse aorta constriction ("pressure overload"), heterozygotes exhibit a higher increase in peak LVP and EDP as well a notable increase in dP/dt, indicating enhanced cardiac systolic function

• echocardiography indicates that ejection fraction is reduced by pressure overload in wild-type but not in heterozygous mutant mice

abnormal cardiac muscle relaxation ( J:75050 )

• at 3 wks after transverse aorta constriction (""pressure overload""), heterozygotes show a higher increase in minimal dP/dt than wild-type mice

• however, heterozygotes display a diastolic dip and plateau pattern of LVP, suggesting "restrictive" diastolic dysfunction; pseudonormalization of LV inflow pattern characterized by increased E wave and short deceleration time of early diastolic transmitral velocity is only observed in heterozygotes

increased left ventricle diastolic pressure ( J:75050 )

• heterozygotes exhibit no significant differences in LV end-diastolic pressure relative to wild-type mice

• however, at 3 wks after transverse aorta constriction (""pressure overload""), heterozygotes exhibit a higher increase in peak EDP relative to wild-type mice

increased left ventricle systolic pressure ( J:75050 )

• heterozygotes exhibit no significant differences in systolic LVP relative to wild-type mice

• however, at 3 wks after transverse aorta constriction (""pressure overload""), heterozygotes exhibit a higher increase in peak LVP relative to wild-type mice

muscle

heart left ventricle hypertrophy ( J:75050 )

• heterozygotes exhibit no significant differences in cardiac morphology e.g. interventricular septal wall thickness, LV posterior wall thickness, LV end-diastolic dimension, or LV end-systolic dimension relative to wild-type mice

• however, at 3 wks after transverse aorta constriction (""pressure overload""), heterozygotes show a higher increase in left ventricular weight to body weight ratio and in LV wall thickness than wild-type mice

increased ventricle muscle contractility ( J:75050 )

• heterozygotes exhibit normal baseline cardiac functions with no significant differences in systolic left ventricular pressure (LVP), end-diastolic pressure (EDP), and positive and negative first derivatives of left ventricular pressure (dP/dt, -dP/dt) relative to wild-type mice

• however, at 3 wks after transverse aorta constriction ("pressure overload"), heterozygotes exhibit a higher increase in peak LVP and EDP as well a notable increase in dP/dt, indicating enhanced cardiac systolic function

• echocardiography indicates that ejection fraction is reduced by pressure overload in wild-type but not in heterozygous mutant mice

abnormal cardiac muscle relaxation ( J:75050 )

• at 3 wks after transverse aorta constriction (""pressure overload""), heterozygotes show a higher increase in minimal dP/dt than wild-type mice

• however, heterozygotes display a diastolic dip and plateau pattern of LVP, suggesting "restrictive" diastolic dysfunction; pseudonormalization of LV inflow pattern characterized by increased E wave and short deceleration time of early diastolic transmitral velocity is only observed in heterozygotes

impaired smooth muscle contractility ( J:65985 )

• upon Na⁺ removal, aortic rings from adult heterozygotes show a significant reduction in vascular tension (36% of high K⁺-induced tension) relative to wild-type rings (94% of high K⁺-induced tension); unlike wild-type, smooth muscle relaxation of heterozygous aortic rings is extracellular Na⁺-independent

growth/size/body

heart left ventricle hypertrophy ( J:75050 )

• heterozygotes exhibit no significant differences in cardiac morphology e.g. interventricular septal wall thickness, LV posterior wall thickness, LV end-diastolic dimension, or LV end-systolic dimension relative to wild-type mice

• however, at 3 wks after transverse aorta constriction (""pressure overload""), heterozygotes show a higher increase in left ventricular weight to body weight ratio and in LV wall thickness than wild-type mice

cellular

cardiac interstitial fibrosis ( J:75050 )

• at 3 wks after transverse aorta constriction (""pressure overload""), heterozygous hearts show significantly increased interstitial collagen accumulation relative to wild-type hearts