Phenotypes associated with this allele

• Allele Symbol: Sphk1^tm1Rlp
• Allele Name: targeted mutation 1, Richard L Proia
• Allele ID: MGI:3526071
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sphk1^tm1Rlp/Sphk1^tm1Rlp	involves: 129S6/SvEvTac	MGI:4822462
hm2	Sphk1^tm1Rlp/Sphk1^tm1Rlp	involves: 129S6/SvEvTac * C57BL/6	MGI:3526401
cx3	Sphk1^tm1Rlp/Sphk1^tm1Rlp Sphk2^tm1Rlp/Sphk2^tm1Rlp	involves: 129S6/SvEvTac * C57BL/6	MGI:3611327

Genotype
MGI:4822462

hm1

• Allelic Composition: Sphk1^tm1Rlp/Sphk1^tm1Rlp
• Genetic Background: involves: 129S6/SvEvTac

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

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:133917 )

• mutants are protected from LPS lethality

immune system

abnormal cytokine level ( J:133917 )

• increase in IL-1beta levels in mesenteric lymph nodes but reduced levels in the lungs after LPS challenge

enlarged mesenteric lymph nodes ( J:133917 )

• mesenteric lymph nodes are 3 times larger than in wild-type 18 hours after LPS challenge

decreased susceptibility to endotoxin shock ( J:133917 )

• mutants exhibit a similar level of initial development of inflammation as wild-type mice in response to severe challenge with lipopolysaccharide (LPS), however attenuation of the inflammation occurs 18 hours after challenge while wild-type mice succumb to the infection

homeostasis/metabolism

abnormal cytokine level ( J:133917 )

• increase in IL-1beta levels in mesenteric lymph nodes but reduced levels in the lungs after LPS challenge

Genotype
MGI:3526401

hm2

• Allelic Composition: Sphk1^tm1Rlp/Sphk1^tm1Rlp
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

normal phenotype

no abnormal phenotype detected ( J:95168 )

• homozygous null mice are viable, fertile, and without any obvious abnormalities, however serum and plasma levels of sphingosine-1-phosphate were reduced to less than 50% of wild-type

Genotype
MGI:3611327

cx3

• Allelic Composition: Sphk1^tm1Rlp/Sphk1^tm1Rlp; Sphk2^tm1Rlp/Sphk2^tm1Rlp
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:103755 )

• 17% of embryos are not viable at E11.5, 70% die by E12.5 and none survive past E13.5

cardiovascular system

abnormal blood vessel morphology ( J:103755 )

• remodeling defects of blood vessels in the head are apparent at E10.5. showing the formation of enlarged, dilated blood vessels and an aberrant anastomotic network

abnormal dorsal aorta morphology ( J:103755 )

• wall of the dorsal aorta is poorly developed at E11.5

abnormal vascular endothelial cell morphology ( J:103755 )

• endothelial cells are severely defective in all blood vessels in the mesenchymal region of the head and some contain vacuoles

abnormal vascular smooth muscle morphology ( J:103755 )

• the smooth muscle covering of the aorta is patchy and incomplete

hemorrhage ( J:103755 )

• severely affected embryos exhibit widespread hemorrhaging in areas other than the brain such as the spinal cord and mandible

hemopericardium ( J:103755 )

• seen in some embryos

intracranial hemorrhage ( J:103755 )

• exhibit cranial hemorrhage by E11.5 and E12.5, predominately in the cranial mesenchymal region

intraventricular hemorrhage ( J:103755 )

• hemorrhaging in the cranial mesenchymal region is sometimes accompanied by intraventricular hemorrhages

spinal hemorrhage ( J:103755 )

• seen in some embryos

muscle

abnormal vascular smooth muscle morphology ( J:103755 )

• the smooth muscle covering of the aorta is patchy and incomplete

nervous system

intracranial hemorrhage ( J:103755 )

• exhibit cranial hemorrhage by E11.5 and E12.5, predominately in the cranial mesenchymal region

intraventricular hemorrhage ( J:103755 )

• hemorrhaging in the cranial mesenchymal region is sometimes accompanied by intraventricular hemorrhages

spinal hemorrhage ( J:103755 )

• seen in some embryos

increased hindbrain apoptosis ( J:103755 )

• apoptosis is increased in the neuroepithelium of the rhombencephalon

increased midbrain apoptosis ( J:103755 )

• apoptosis is increased in the neuroepithelium of the mesencephalon

increased embryonic neuroepithelium apoptosis ( J:103755 )

• apoptosis is increased in the neuroepithelium of the mesencephalon and the rhombencephalon

abnormal embryonic neuroepithelium morphology ( J:103755 )

• embryos exhibit a very thin, poorly developed wall of neuroepithelium and an irregularly shaped neuroepithelial layer in the whole brain

decreased embryonic neuroepithelium thickness ( J:103755 )

• embryos exhibit a very thin, poorly developed wall of neuroepithelium

incomplete rostral neuropore closure ( J:103755 )

• impaired anterior neural tube closure

dilated brain ventricle ( J:103755 )

• ventricular dilation at E11.5

exencephaly ( J:103755 )

• seen in 18% of embryos at E10.5, 13% at E11.5 and in 20% at E12.5, however do not observe spina bifida

embryo

abnormal embryonic neuroepithelium morphology ( J:103755 )

• embryos exhibit a very thin, poorly developed wall of neuroepithelium and an irregularly shaped neuroepithelial layer in the whole brain

decreased embryonic neuroepithelium thickness ( J:103755 )

• embryos exhibit a very thin, poorly developed wall of neuroepithelium

incomplete rostral neuropore closure ( J:103755 )

• impaired anterior neural tube closure

homeostasis/metabolism

hemopericardium ( J:103755 )

• seen in some embryos

cellular

increased hindbrain apoptosis ( J:103755 )

• apoptosis is increased in the neuroepithelium of the rhombencephalon

increased midbrain apoptosis ( J:103755 )

• apoptosis is increased in the neuroepithelium of the mesencephalon

increased embryonic neuroepithelium apoptosis ( J:103755 )

• apoptosis is increased in the neuroepithelium of the mesencephalon and the rhombencephalon