Phenotypes associated with this allele

• Allele Symbol: S1pr1^tm1Rlp
• Allele Name: targeted mutation 1, Richard L Proia
• Allele ID: MGI:2158346
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	S1pr1^tm1Rlp/S1pr1^tm1Rlp	involves: 129S6/SvEvTac	MGI:3611330
hm2	S1pr1^tm1Rlp/S1pr1^tm1Rlp	involves: 129S6/SvEvTac * C57BL/6	MGI:3611325
cn3	S1pr1^tm1Rlp/S1pr1^tm2Rlp Tg(Tek-cre)1Ywa/?	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:2681954
cx4	S1pr1^tm1Rlp/S1pr1^tm1Rlp S1pr2^tm1Rlp/S1pr2^tm1Rlp	involves: 129S6/SvEvTac * C57BL/6	MGI:3621361
cx5	S1pr1^tm1Rlp/S1pr1^tm1Rlp S1pr3^tm1Rlp/S1pr3^tm1Rlp	involves: 129S6/SvEvTac * C57BL/6	MGI:3621362
cx6	S1pr1^tm1Rlp/S1pr1^tm1Rlp S1pr3^tm1Rlp/S1pr3^tm1Rlp S1pr2^tm1Rlp/S1pr2^tm1Rlp	involves: 129S6/SvEvTac * C57BL/6	MGI:3621363

Genotype
MGI:3611330

hm1

• Allelic Composition: S1pr1^tm1Rlp/S1pr1^tm1Rlp
• Genetic Background: involves: 129S6/SvEvTac

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:189010 )

• rapid demise and synchronous death of the embryos between E13.5 and E14

cardiovascular system

abnormal artery morphology ( J:189010 )

• glomeruloid lesions are also seen on the femoral, tail, and intercostal arteries

• glomeruloid lesions contain abundant mural cells and basement membrane proteins

abnormal aorta morphology ( J:189010 )

• abnormal microvasculature around the aorta that forms glomeruloid lesions with numerous ectopic endothelium-lined connections to the aortic lumen

• at E11.5 lesions are mainly concentrated on the dorsal side of the aorta, by E12.5 lesions often occur in lateral regions as well, and by E13.5 lesions frequently surround the aortic circumference

abnormal aorta endothelium morphology ( J:189010 )

• massive endothelial hyperplasia

abnormal aorta smooth muscle morphology ( J:189010 )

• coverage of the aorta is abnormal

abnormal vascular branching morphogenesis ( J:189010 )

• increase in the number of endothelial tip cells, protrusions of endothelial filopodia, and overall vascular density (endothelial hyper-sprouting) is detected from E11.5 onward in the hindbrain, neural tube and limb vasculature

hemorrhage ( J:103755 )

increased vascular endothelial cell apoptosis ( J:189010 )

• at E13.5 massive induction of apoptosis is seen in endothelial cells

nervous system

increased neuron apoptosis ( J:189010 )

• at E13.5 massive induction of apoptosis is seen in the dorsal root ganglia

abnormal forebrain morphology ( J:103755 )

• massive cell loss in the forebrain at E12.5

abnormal diencephalon morphology ( J:103755 )

• increase in apoptotic cells in the neuroepithelial layers of the diencephalons at E12.5

abnormal telencephalon morphology ( J:103755 )

• increase in apoptotic cells in the neuroepithelial layers of the telencephalon and a decrease in mitotic cell numbers at E12.5

immune system

abnormal NK cell differentiation ( J:154069 )

• in reconstitution experiments, derived NK cells accumulate in the lymph nodes and bone marrow indicating a reduction in NK cell egression from the lymph nodes and bone marrow compared to when wild-type bone marrow is used

• egression of NK cells from the bone marrow into the bone marrow sinusoids is impaired compared to in wild-type mice

decreased NK cell number ( J:154069 )

• in the bone marrow sinusoids

hematopoietic system

abnormal NK cell differentiation ( J:154069 )

• in reconstitution experiments, derived NK cells accumulate in the lymph nodes and bone marrow indicating a reduction in NK cell egression from the lymph nodes and bone marrow compared to when wild-type bone marrow is used

• egression of NK cells from the bone marrow into the bone marrow sinusoids is impaired compared to in wild-type mice

decreased NK cell number ( J:154069 )

• in the bone marrow sinusoids

cellular

increased vascular endothelial cell apoptosis ( J:189010 )

• at E13.5 massive induction of apoptosis is seen in endothelial cells

increased neuron apoptosis ( J:189010 )

• at E13.5 massive induction of apoptosis is seen in the dorsal root ganglia

muscle

abnormal aorta smooth muscle morphology ( J:189010 )

• coverage of the aorta is abnormal

Genotype
MGI:3611325

hm2

• Allelic Composition: S1pr1^tm1Rlp/S1pr1^tm1Rlp
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

Bleeding phenotypes of mice carrying different combinations of deleted S1p receptors

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:71961 , J:106055 )

• die between E12.5 and E14.5; no surviving mutants past E14.5 (J:71961)

embryo

abnormal visceral yolk sac morphology ( J:71961 )

• yolk sacs display progressive edema and normal vasculature but with less blood

cardiovascular system

abnormal blood vessel morphology ( J:71961 )

• exhibit a defect in blood vessel maturation, however vasculogenesis and angiogenesis appear normal

• small vessels in the forebrain are dilated

abnormal vascular endothelial cell morphology ( J:71961 )

• endothelial cell body is very thin and in some areas, fragmented, resulting in a discontinuous endothelial cell layer

• endothelial cell nuclei of capillaries are abnormally rounded and enlarged

abnormal pericyte morphology ( J:71961 )

• reduction of pericytes in vessels and absence of capillary pericytes

abnormal vascular smooth muscle morphology ( J:71961 )

• exhibit vascular smooth muscle defects, with aortae and intracerebral arteries covered only ventrally by poorly organized vascular smooth muscle cells which are not present along the dorsal surface, however muscular layers in the gastrointestinal tract and bronchial tree are normal

vascular smooth muscle hypoplasia ( J:71961 )

pericardial edema ( J:71961 )

• seen at E12.5 and E13.5

enlarged pericardium ( J:71961 )

hemorrhage ( J:71961 , J:106055 )

• intraembryonic bleeding is evident at E12.5 and is widespread at E13.5 (J:71961)

• bleeding along the body and head at E12.5 (J:106055)

muscle

abnormal vascular smooth muscle morphology ( J:71961 )

• exhibit vascular smooth muscle defects, with aortae and intracerebral arteries covered only ventrally by poorly organized vascular smooth muscle cells which are not present along the dorsal surface, however muscular layers in the gastrointestinal tract and bronchial tree are normal

vascular smooth muscle hypoplasia ( J:71961 )

homeostasis/metabolism

edema ( J:71961 )

• severe edema throughout the body at E13.5

pericardial edema ( J:71961 )

• seen at E12.5 and E13.5

limbs/digits/tail

abnormal limb morphology ( J:71961 , J:106055 )

• limbs are underdeveloped and rounded with areas of bleeding (J:71961)

cellular

impaired fibroblast cell migration ( J:71961 )

• fibroblasts do not display a significant migratory response to sphingosine-1-phosphate as in wild-type

Genotype
MGI:2681954

cn3

• Allelic Composition: S1pr1^tm1Rlp/S1pr1^tm2Rlp; Tg(Tek-cre)1Ywa/?
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

Discontinuous smooth muscle cell coverage around the aorta in S1pr1^tm1Rlp/S1pr1^tm2Rlp Tg(Tek-cre)1Ywa/? mice

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:86450 )

• died before birth and by E14.5 no heartbeat is seen

cardiovascular system

abnormal cardiovascular system morphology ( J:86450 )

poor arterial differentiation ( J:86450 )

• vascular smooth muscle only on ventral side of aorta and vessels of the brain

• dorsal side of aorta incompletely covered with endothelium

abnormal aorta smooth muscle morphology ( J:106055 )

• discontinuous smooth muscle cell coverage is seen around the aorta

abnormal pericardial cavity morphology ( J:86450 )

• enlarged pericardial cavity at E12.5

abnormal cardiovascular system physiology ( J:86450 )

hemorrhage ( J:86450 )

• spots of bleeding on the body by E12.5

• by E13.5, massive bleeding was occuring

embryo

abnormal visceral yolk sac morphology ( J:86450 )

• by E12.5, yolk sac was edematous

• less blood than normal in vessels

limbs/digits/tail

abnormal limb morphology ( J:86450 )

• limbs underdeveloped and rounded at E12.5

muscle

abnormal aorta smooth muscle morphology ( J:106055 )

• discontinuous smooth muscle cell coverage is seen around the aorta

Genotype
MGI:3621361

cx4

• Allelic Composition: S1pr1^tm1Rlp/S1pr1^tm1Rlp; S1pr2^tm1Rlp/S1pr2^tm1Rlp
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

Bleeding phenotypes of mice carrying different combinations of deleted S1p receptors

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:106055 )

• die between E10.5 and E12.5

cardiovascular system

abnormal angiogenesis ( J:106055 )

• at E10.5, vasculature in the head is less mature with fewer branches in the capillary network

hemorrhage ( J:106055 )

• bleeding along the body and head at E10.5

Genotype
MGI:3621362

cx5

• Allelic Composition: S1pr1^tm1Rlp/S1pr1^tm1Rlp; S1pr3^tm1Rlp/S1pr3^tm1Rlp
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

Bleeding phenotypes of mice carrying different combinations of deleted S1p receptors

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:106055 )

• die between E12.5 and E13.5

cardiovascular system

hemorrhage ( J:106055 )

• bleeding along the body and head at E12.5

limbs/digits/tail

abnormal limb morphology ( J:106055 )

• underdeveloped limbs at E12.5

Genotype
MGI:3621363

cx6

• Allelic Composition: S1pr1^tm1Rlp/S1pr1^tm1Rlp; S1pr3^tm1Rlp/S1pr3^tm1Rlp; S1pr2^tm1Rlp/S1pr2^tm1Rlp
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

Immature vascular network in S1pr1^tm1Rlp/S1pr1^tm1Rlp S1pr2^tm1Rlp/S1pr2^tm1Rlp and S1pr1^tm1Rlp/S1pr1^tm1Rlp S1pr2^tm1Rlp/S1pr2^tm1Rlp S1pr3^tm1Rlp/S1pr3^tm1Rlp embryos

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:106055 )

• die between E10.5 and E11.5

cardiovascular system

abnormal angiogenesis ( J:106055 )

• at E10.5, vasculature in the head is less mature with fewer branches in the capillary network

hemorrhage ( J:106055 )

• bleeding along the body and head in 50% of embryos at E10.5