Mouse Genome Informatics
hm1
    Gabrb3tm1Geh/Gabrb3tm1Geh
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 30% with normal palates die neonatally
• 90% die within 1 day of birth
• animals surviving to birth live an average of 18 weeks

growth/size/body
• about 57% exhibit cleft palate
• 5-10% that survive to adulthood are runted until weaning but achieve normal body weight by adulthood

behavior/neurological
• have difficulty walking on grids and repeatedly fall off platforms and rotarods
• have difficulty swimming
• many have been observed to run continuously in tight circles for extended periods of time (J:39801)
• hyperresponsive to human contact and other sensory stimuli
• failure to nuture offspring
• variable severity of epileptic seizures in mice over 10 weeks of age

hearing/vestibular/ear
• at >24 weeks, homozygotes exhibit basal-turn histopathology
• rarity and fragility of homozygotes prevented evaluation of cochlear histopathology at 6 weeks, as none were killed at this age
• at >24 weeks, homozygotes display a significant reduction in the density of IHC afferent innervation relative to age-matched wild-type mice, indicating neuropathy
• at ~24 weeks, homozygotes display a nearly complete loss of IHCs throughout the basal 15% of the cochlear spiral, i.e., from 40 to 90 kHz according to the mouse cochlear frequency map
• at >24 weeks, homozygotes display a reduction in OHC efferent innervation, with fewer efferent axons crossing to OHCs at the level of the tunnel of Corti relative to age-matched wild-type mice
• at ~24 weeks, homozygotes display a nearly complete loss of OHCs throughout the basal 15% of the cochlear spiral, i.e., from 40 to 90 kHz according to the mouse cochlear frequency map
• at >24 weeks, homozygotes display widespread loss of type IV fibrocytes, spreading farther apically
• at 6 weeks, suprathreshold ABR amplitudes in homozygotes are significantly reduced in amplitude, by at least 50% at all test frequencies and sound levels
• at 6 weeks, homozygotes display severe cochlear dysfunction, as shown by highly significant ABR threshold elevations of 20-45 dB across a range of test frequencies, with peak loss occurring at 22.6 kHz
• ABR threshold elevation corresponds to >2 orders of magnitude of stimulus amplitude
• at 6 weeks, homozygotes display significantly elevated DPOAE thresholds across all test frequencies relative to wild-type mice, with DPOAE thresholds of >60 dB at high frequencies
• at 16 kHz (middle cochlear region), ABR shifts are similar in magnitude to the observed DPOAE shifts, suggesting that the threshold shift arises at, or before, the stage of OHC transduction and amplification

nervous system
• variable severity of epileptic seizures in mice over 10 weeks of age
• at >24 weeks, homozygotes display a significant reduction in the density of IHC afferent innervation relative to age-matched wild-type mice, indicating neuropathy
• at ~24 weeks, homozygotes display a nearly complete loss of IHCs throughout the basal 15% of the cochlear spiral, i.e., from 40 to 90 kHz according to the mouse cochlear frequency map
• at >24 weeks, homozygotes display a reduction in OHC efferent innervation, with fewer efferent axons crossing to OHCs at the level of the tunnel of Corti relative to age-matched wild-type mice
• at ~24 weeks, homozygotes display a nearly complete loss of OHCs throughout the basal 15% of the cochlear spiral, i.e., from 40 to 90 kHz according to the mouse cochlear frequency map
• at >24 weeks, homozygotes show partial loss of spiral ganglion cells but only in cochlear regions in which IHCs are degenerated
• mutant calretinin-negative cells are smaller at each sampled location in the spiral ganglion relative to wild-type cells
• the reduction in mean somatic area of mutant calretinin-negative cells is 5.2% in the basal turn, 8.7% in the middle turn, and 12.2% in the apical turn of the spiral ganglion relative to wild-type cells
• adult homozygotes display significantly smaller cochlear ganglion cell areas at every sampled region in the spiral ganglion, except the apical cochlear turn
• in contrast, mutant calretinin-positive ganglion cells are of normal size and proportion relative to wild-type cells
• adult homozygotes show hypoplasia of spiral ganglion cells in the middle and basal turns of the cochlea, while the apical turn remains unaffected
• spiral ganglion cell hypoplasia is strictly due to a size reduction of calretinin-negative ganglion cells
• adult homozygotes display significantly smaller ganglion cell areas in both divisions of Scarpa's ganglion (superior and inferior) relative to wild-type mice
• mutant calretinin-negative cells are smaller in both divisions of Scarpa's ganglion relative to wild-type cells
• the reduction in mean somatic area of mutant calretinin-negative cells is 9.5% in the inferior division and 21.5% in the superior division of Scarpa's ganglion
• in contrast, mutant calretinin-positive ganglion cells are of normal size and proportion relative to wild-type cells
• adult homozygotes show ganglion cell hypoplasia in both divisions of Scarpa's ganglion
• Scarpa ganglion cell hypoplasia is strictly due to a size reduction of calretinin-negative ganglion cells
• at >24 weeks, homozygotes display clear signs of cochlear nerve abnormalities (progressive loss of afferent terminals)
• 80% decrease in the maximal amplitude of GABA-activated chloride currents in dorsal root ganglion

craniofacial
• about 57% exhibit cleft palate

digestive/alimentary system
• about 57% exhibit cleft palate

skeleton
• at >24 weeks, homozygotes display widespread loss of type IV fibrocytes, spreading farther apically


Mouse Genome Informatics
hm2
    Gabrb3tm1Geh/Gabrb3tm1Geh
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• frequently seen sleeping away from nesting material
• increased time until first contact with a novel object compared to wild-type
• decreased amount of time spent investigating a novel object compared to wild-type
• total number of rearings differs from wild-type littermates and C57BL/6J mice but not from 129X1/SvJ mice
• the mean duration of each rearing event is decreased compared to controls
• a higher degree of ambulatory activity than control mice
• a higher number of entries, in regards to the total transitions between all chambers, of a social interaction apparatus
• fail to show a significant preference for spending time in the interaction chamber adjacent to the stimulus cage containing an unfamiliar mouse as opposed to spending time in the interaction chamber adjacent to an empty stimulus cage
• mice fail to exhibit a preference for interacting with a new mouse over a familiar mouse
• at 1, 24 and 48 hours after introduction of new nestlet material, mice utilize significantly less material than wild-type controls
• significant impairment in their ability to achieve the nest complexity exhibited by the controls
• location of nest construction is different

nervous system
• significant decrease in the surface area
• significant decrease in the surface area
• significant decrease in the surface area
• significant decrease in the surface area
• significant decrease in the surface area
• significant decrease in the surface area

Mouse Models of Human Disease
OMIM IDRef(s)
Autism 209850 J:130259