Phenotypes Associated with This Genotype

Genotype
MGI:3692665

• Allelic Composition: S1pr2^tm1Ajml/S1pr2^tm1Ajml
• Genetic Background: either: (involves: 129S5/SvEvBrd) or (involves: 129S5/SvEvBrd * C57BL/6)

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

mortality/aging

premature death ( J:112371 )

• Background Sensitivity: on a 50:50 129SvEvBrd:C57BL/6 background homozygotes exhibit a ~15% overall death rate from seizures; however, on a pure 129SvEvBrd background the overall death rate drops below 5%

behavior/neurological

impaired swimming ( J:112371 )

• 42.9% of aging homozygotes (aged 70 days or older) exhibit impaired swimming ability, in the absence of overt motor dysfunction

head tilt ( J:112371 )

• 45.7% of aging homozygotes (aged 70 days or older) exhibit tilted heads

seizures ( J:112371 )

• Background Sensitivity: on a 50:50 129SvEvBrd:C57BL/6 background, some homozygotes display rare (mean <4 during lifespan), brief (mean <5 s) seizures; on a pure 129SvEvBrd background, the period of seizure susceptibility is reduced by ~75%; no seizures and death are noted on a purified C57BL/6NCrlBr background

hearing/vestibular/ear

otosclerosis ( J:112371 )

• occasional otosclerosis is detected well after the onset of hearing loss

detached Reissner membrane ( J:112371 )

• in some cases, Reissner's membrane exits distant from its typical emergence from the upper limit of the stria vascularis

• in other cases, it appears to be partially collapsed over the stria vascularis

abnormal Rosenthal canal morphology ( J:112371 )

• Rosenthal's canal is progressively and completely depleted of cell bodies and processes with increasing age

cochlear outer hair cell degeneration ( J:112371 , J:231927 )

• cochlear OHCs are lost with increasing age to a greater extent than in control inner ears (J:112371)

organ of Corti degeneration ( J:112371 )

• by 3 weeks, the tunnel of Corti/Nuel's space structures are consistently abnormal

• with time, many structures of the organ of Corti are completely lost

thin stria vascularis ( J:112371 , J:231927 )

• aging homozygotes exhibit a much thinner stria vascularis (J:112371)

abnormal tectorial membrane morphology ( J:112371 )

• in older homozygotes, the tectorial membrane is encased in a membrane-like cover, shows fiber-like striations, and is tilted from the site where the organ of Corti would lie

• commonly, epithelial-like cells form "nests" at the site where Reissner's membrane and the tectorial membrane lie together in both basal and apical cochlear turns

• basal cochlear turns are more affected, consistent with the only ABR signal from mutant mice being in response to the lowest frequency tone

small scala media ( J:112371 )

• the scala media portion of the cochlear labyrinth is reduced with increasing age

vestibular saccular degeneration ( J:112371 )

• at one year, homozygotes display significant saccular degeneration

decreased otolith number ( J:112371 , J:231927 )

• aging homozygotes display decreases in the otoconia of both the utricle and saccule relative to age-matched controls (J:112371)

• loss of utricular otoconia precedes the vestibular defects (head tilt and swimming) and does not predict the behavioral defects as well as the loss of saccular otoconia (J:112371)

increased or absent threshold for auditory brainstem response ( J:112371 )

• homozygotes show no ABR responses at 100 dB (highest intensity tested); the threshold, were there to be any response, would thus be >100 dB

deafness ( J:112371 , J:231927 )

• as early as P22, 100% of homozygotes are profoundly deaf, as shown by lack of auditory evoked brainstem (ABR) responses, while the vestibular defects are present in 40-50% of mutant mice (J:112371)

• at P22, one homozygote showed a slight response to very high intensity (90 dB) 8 kHz tones but failed to respond to 100 dB clicks, 16 kHz tones or 32 kHz tones; all other homozygotes failed to respond to all tones and clicks (J:112371)

• both old and young homozygotes fail to display any of the expected ABR peaks, suggesting defects in peripheral components of the auditory system (J:112371)

abnormal vestibular system physiology ( J:112371 )

• aging homozygotes show signs of vestibular dysfunction e.g. head tilt and impaired swimming

nervous system

seizures ( J:112371 )

• Background Sensitivity: on a 50:50 129SvEvBrd:C57BL/6 background, some homozygotes display rare (mean <4 during lifespan), brief (mean <5 s) seizures; on a pure 129SvEvBrd background, the period of seizure susceptibility is reduced by ~75%; no seizures and death are noted on a purified C57BL/6NCrlBr background

cochlear outer hair cell degeneration ( J:112371 , J:231927 )

• cochlear OHCs are lost with increasing age to a greater extent than in control inner ears (J:112371)

skeleton

otosclerosis ( J:112371 )

• occasional otosclerosis is detected well after the onset of hearing loss

craniofacial

otosclerosis ( J:112371 )

• occasional otosclerosis is detected well after the onset of hearing loss

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive nonsyndromic deafness 68		DOID:0110519	OMIM:610419	J:231927