Phenotypes Associated with This Genotype

Genotype
MGI:7282200

• Allelic Composition: Gas2^{tm1a(EUCOMM)Hmgu}/Gas2^{tm1a(EUCOMM)Hmgu}
• Genetic Background: C57BL/6N-Gas2^{tm1a(EUCOMM)Hmgu}

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

hearing/vestibular/ear

decreased cochlear outer hair cell number ( J:306028 )

• small, but progressive loss of outer hair cells, resulting in a 10% decrease in outer hair cell number by P60

• however, cochlear anatomy appears normal

abnormal organ of Corti supporting cell morphology ( J:306028 )

• mice show defects in supporting cell microtubules

• cochlear supporting cells are less stiff; cochlear explants grown in culture do not show an increase in stiffness across pillar and outer hair cell rows over time as seen in control explants

abnormal Deiters cell morphology ( J:306028 )

• Deiters cell microtubules are severely disorganized and less tightly bundled, especially at P12 and P14

• Deiters cell phalangeal processes are buckled and show increased tortuosity

• however, total number of microtubules does not differ despite reduced tubule density

abnormal pillar cell morphology ( J:306028 )

• heads of inner pillar cells show a progressive destabilization of microtubule bundles beginning at P14 such that by P25, nearly 70% of microtubules are depleted from the inner pillar cell heads and almost completely absent at P60; a small but significant reduction in microtubules is also seen in outer pillar cells

• the number, density, and organization of pillar cell microtubules is greatly reduced and the cross-links between microtubule and actin are mostly absent at P25

abnormal hearing physiology ( J:306028 )

• transmission of sound-evoked vibrations is impaired such that the frequency range over which cochlear amplification occurs on the basilar membrane is reduced indicating less longitudinal coupling

increased or absent threshold for auditory brainstem response ( J:306028 )

• mice show elevated auditory brainstem responses (ABR) across all frequencies tested at 2 months of age, with the most pronounced threshold shifts detected at higher frequencies

• however, endocochlear potential is not altered

abnormal distortion product otoacoustic emission ( J:306028 )

• distortion product otoacoustic emissions (DPOAEs) are reduced by 10 to 20 dB

impaired hearing ( J:306028 )

• mice exhibit severe hearing loss

• however, mice show no overt signs of inner ear dysmorphology and hair and supporting cells form in the correct number and position, spiral ganglion neurons innervate appropriate sensory targets, and cellular organization in the organ of Corti is maintained, and no differences in stria vascularis morphology are seen

nervous system

decreased cochlear outer hair cell number ( J:306028 )

• small, but progressive loss of outer hair cells, resulting in a 10% decrease in outer hair cell number by P60

• however, cochlear anatomy appears normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
sensorineural hearing loss		DOID:10003		J:306028