All Phenotypes S1pr2<tm1Jch> MGI Mouse

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

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

• 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

decreased litter size ( J:77809 )

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

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