Phenotypes Associated with This Genotype

Genotype
MGI:3639338

• Allelic Composition: Hpn^tm1Qwu/Hpn^tm1Qwu
• Genetic Background: involves: 129X1/SvJ * NIH Swiss

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

hearing/vestibular/ear

abnormal tectorial membrane morphology ( J:123922 )

• at P8 or later, the tectorial membrane appears deformed with a reduced limbal attachment zone and large holes within its matrix

abnormal tectorial membrane striated-sheet matrix morphology ( J:123922 )

• at P8 or later, the tectorial membrane has large holes within its matrix

enlarged tectorial membrane ( J:123922 )

• at P8 or later, the cross-sectional area of the tectorial membrane and longest vertical distance measured between its dorsal and ventral surface are doubled

abnormal cochlear inner hair cell physiology ( J:123922 )

• in adult homozygotes, expression of the Ca²⁺-activated large conductance K⁺ (BK) channel alpha-subunit is significantly reduced in IHCs, suggesting a functional deficit in potassium current within the organ of Corti, despite the absence of IHC loss

abnormal cochlear outer hair cell physiology ( J:123922 )

• in adult homozygotes, expression of the Ca²⁺-activated large conductance K⁺ (BK) channel alpha-subunit is significantly reduced at the base of OHCs, despite the absence of OHC loss

abnormal auditory brainstem response waveform shape ( J:123922 )

• at 7 to 8 weeks of age, homozygotes produce poorly defined click-evoked ABR waveforms when attenuation is set at 0 or 5 dBA

increased or absent threshold for auditory brainstem response ( J:123922 )

• at 7 to 8 weeks of age, homozygotes display no ABR responses at 10, 15, and 20 dBA

• at 7 to 8 weeks of age, homozygotes display a 42 dB sound pressure level threshold increase relative to wild-type or heterozygous mice

impaired hearing ( J:123922 )

• at 7 to 8 weeks of age, homozygotes exhibit profound hearing loss

homeostasis/metabolism

decreased thyroxine level ( J:123922 )

• at 7 weeks of age, homozygotes show a 43% reduction in free thyroxine (T4) levels in serum relative to wild-type mice

increased circulating alkaline phosphatase level ( J:45393 )

• homozygotes of both sexes exhibit a ~2-fold increase in serum concentrations of bone-derived alkaline phosphatase relative to wild-type littermates

• however, homozygotes are viable and fertile, with no significant differences in major organ histology, skeletal morphology, blood coagulation, liver weight, serum concentration of liver-derived proteins or response to induced septic shock relative to wild type littermates

nervous system

abnormal cochlear inner hair cell physiology ( J:123922 )

• in adult homozygotes, expression of the Ca²⁺-activated large conductance K⁺ (BK) channel alpha-subunit is significantly reduced in IHCs, suggesting a functional deficit in potassium current within the organ of Corti, despite the absence of IHC loss

abnormal cochlear outer hair cell physiology ( J:123922 )

• in adult homozygotes, expression of the Ca²⁺-activated large conductance K⁺ (BK) channel alpha-subunit is significantly reduced at the base of OHCs, despite the absence of OHC loss

abnormal cochlear ganglion morphology ( J:123922 )

• homozygotes show abnormal compaction of the soma and fibers of spiral ganglion neurons, with empty spaces found between spiral ganglion neurons and Schwann cells

• however, no cell loss occurs, as spiral ganglion neuron and Schwann cell densities remain normal

• this compaction defect appears to be associated with a specific down-regulation of expression of myelin basic protein (MBP) and myelin protein zero (P0) along the peripheral portion of the auditory nerve

abnormal myelination ( J:123922 )

• adult homozygotes display defective myelination of the auditory nerve, resulting in abnormal compaction of spiral ganglion neurons

endocrine/exocrine glands

decreased activity of thyroid gland ( J:123922 )

• adut homozygotes are hypothyroidic