Phenotypes associated with this allele

• Allele Symbol: S1pr3^tm1Jch
• Allele Name: targeted mutation 1, Jerold Chun
• Allele ID: MGI:2182637
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	S1pr3^tm1Jch/S1pr3^tm1Jch	involves: 129S1/Sv * 129X1/SvJ	MGI:4822464
hm2	S1pr3^tm1Jch/S1pr3^tm1Jch	involves: 129S1/Sv * 129X1/SvJ * C57BL/6N	MGI:3663161
cx3	S1pr2^tm1Jch/S1pr2^tm1Jch S1pr3^tm1Jch/S1pr3^tm1Jch	involves: 129S1/Sv * 129X1/SvJ * C57BL/6N	MGI:3689741
cx4	S1pr3^tm1Jch/S1pr3^+ S1pr2^tm1Jch/S1pr2^tm1Jch	involves: 129S1/Sv * 129X1/SvJ * C57BL/6N	MGI:3700733

Genotype
MGI:4822464

hm1

• Allelic Composition: S1pr3^tm1Jch/S1pr3^tm1Jch
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

• ♀: 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

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

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 are protected from lipopolysaccharide (LPS) induced lethality

Genotype
MGI:3663161

hm2

• Allelic Composition: S1pr3^tm1Jch/S1pr3^tm1Jch
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6N

reproductive system

decreased litter size ( J:71372 )

• litter sizes from homozygous intercrosses are significantly smaller than those from crosses between heterozygous males and wild-type females (5.6 vs 7.5 pups/litter)

• however, homozygotes exhibit normal embryonic development, general health, body weight, fertility, hematology, tissue histology and longevity relative to wild-type mice

cellular

abnormal cell physiology ( J:71372 )

• MEFs obtained from E14 mutant embryos exhibit significant decreases in phospholipase C activation, slight decreases in adenylyl cyclase inhibition, and no change in Rho activation relative to wild-type MEFs

respiratory system

abnormal pulmonary alveolus epithelial cell morphology ( J:99867 )

• resistant to pulmonary edema induced by intratracheal injection of sphingosine 1 phosphate

• lung epithelial cells maintain tight junctions between one another after sphingosine 1 phosphate treatment whereas control cells will retract from one another opening clear paracellular gaps between the airway surface and the subepithelial extracellular matrix

• TNF effect to enhance pulmonary edema is blocked

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:118369 )

N • homozygotes display a normal startle reflex, responding to acoustic stimuli >90-100 dB

Genotype
MGI:3689741

cx3

• Allelic Composition: S1pr2^tm1Jch/S1pr2^tm1Jch; S1pr3^tm1Jch/S1pr3^tm1Jch
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6N

mortality/aging

perinatal lethality, incomplete penetrance ( J:77809 )

• more than half of pups born from crosses between homozygotes are dead within one week, mostly within 24 hours

• surviving pups grow up normally with no obvious abnormalities at young ages

behavior/neurological

impaired righting response ( J:118369 )

• older double homozygotes become disoriented and often experience a delay in contact righting behavior

absent startle reflex ( J:118369 )

• as early as 4 weeks of age, all double homozygotes completely lack a startle reflex to acoustic stimuli >90-100 dB

limb grasping ( J:118369 )

• as early as 2 months, double homozygotes suspended by the tail curl upward, often landing on their heads when returned to the ground

• this behavior shows an age-related increase in penetrance and occurs uniformly by 6 months of age

impaired swimming ( J:118369 )

• double homozygotes show a progressive loss of swimming ability and are almost uniformly deficient by 18 weeks of age

• in contrast, very young double mutant mice (4 weeks) display no difficulty in the forced swim test

abnormal posture ( J:118369 )

• at >6 months, double homozygotes display consistent postural defects indicative of vestibular dysfunction

head tilt ( J:118369 )

• at >6 months, double homozygotes show a persistent head tilt

decreased vertical activity ( J:118369 )

• at 12-14 weeks of age, double homozygotes show a significant decrease in rearing frequency, fail to maintain balance on their hindlimbs, and arch their backs to elevate their noses

abnormal maternal nurturing ( J:77809 )

♀ • perinatal death of pups due to maternal neglect

reproductive system

decreased litter size ( J:77809 )

• vastly reduced number of progeny from crosses between double null parents

hearing/vestibular/ear

cochlear inner hair cell degeneration ( J:118369 )

• at >2 weeks, double homozygotes display progressive IHC degeneration in a basal-to-apical pattern that is almost complete by 4 months of age

cochlear outer hair cell degeneration ( J:118369 )

• at >2 weeks, double homozygotes display progressive OHC degeneration in a basal-to-apical pattern that is almost complete by 4 months of age

degeneration of organ of Corti supporting cells ( J:118369 )

• at >2 weeks, double homozygotes display progressive degeneration of supporting cells that is almost complete by 4 months of age

organ of Corti degeneration ( J:118369 )

• at >2 weeks of age, double homozygotes show progressive degeneration of the organ of Corti in a basal-to-apical pattern

• however, cochlear hair cell stereociliary bundle morphology is normal at P4, and cochlear histology remains intact until at least 2 weeks of age

abnormal inner ear vestibule morphology ( J:118369 )

• starting at >4 weeks, double homozygotes exhibit a progressive disorganization of the sensory epithelium of vestibular maculas that becomes prominent at 4 months

• by 8 months, the epithelial layer is significantly disorganized and lacks afferent calyces and stereocilia

absent vestibular hair cell stereocilia ( J:118369 )

• older double homozygotes show complete loss of vestibular stereocilia

vestibular hair cell degeneration ( J:118369 )

utricular macular degeneration ( J:118369 )

vestibular saccular macula degeneration ( J:118369 )

abnormal vestibular system physiology ( J:118369 )

• double homozygotes exhibit progressive loss of vestibular function, as shown by impaired swimming, rearing behavior and contact righting

nervous system

cochlear inner hair cell degeneration ( J:118369 )

• at >2 weeks, double homozygotes display progressive IHC degeneration in a basal-to-apical pattern that is almost complete by 4 months of age

cochlear outer hair cell degeneration ( J:118369 )

• at >2 weeks, double homozygotes display progressive OHC degeneration in a basal-to-apical pattern that is almost complete by 4 months of age

absent vestibular hair cell stereocilia ( J:118369 )

• older double homozygotes show complete loss of vestibular stereocilia

vestibular hair cell degeneration ( J:118369 )

cochlear ganglion degeneration ( J:118369 )

• at >2 weeks, double homozygotes exhibit a striking degeneration of afferent neurons in the spiral ganglia, in a basal-to-apical pattern

Genotype
MGI:3700733

cx4

• Allelic Composition: S1pr3^tm1Jch/S1pr3⁺; S1pr2^tm1Jch/S1pr2^tm1Jch
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6N

behavior/neurological

absent startle reflex ( J:118369 )

• as early as 4 weeks of age, all mutant mice homozygous for Edg5^tm1Jch and heterozygous for Edg3^tm1Jch completely lack a startle reflex to acoustic stimuli >90-100 dB