Mouse Genome Informatics
hm1
    Cldn14tm1Tbf/Cldn14tm1Tbf
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
hearing/vestibular/ear
• by P18, some IHCs display abnormal stereocilia
• by P18, OHC stereocilia are completely absent from the cochlear apex
• homozygotes exhibit rapid degeneration of cochlear hair cells during the second and third weeks of life
• cochlear HC degeneration is triggered by altered ionic permeability through the reticular lamina
• homozygotes display slower degeneration of cochlear IHCs, following rapid degeneration of OHCs
• by P18, IHCs are partially missing throughout the cochlea
• at >P7, homozygotes exhibit rapid loss of OHCs progressing from base to apex
• at P10-P13, OHCs are lost or disorganized throughout most of cochlear length, except for the extreme apex
• by P18, only a few OHCs with disorganized stereocilia are present at the most apical cochlear region
• OHC degeneration is first characterized by disorganization and loss of stereocilia, followed by swelling of cell bodies, shortening of cell length, submerging of cell bodies under the reticular lamina, and eventually death
• at 4 weeks, ABR thresholds are elevated by 50 dB-SPL or more over all frequencies tested
• ABR analyses indicate that homozygotes are already deaf by the third postnatal week (P15-P17)
• however, homozygotes exhibit normal endocochlear potential values at 5 and 10 weeks of age

nervous system
• by P18, some IHCs display abnormal stereocilia
• by P18, OHC stereocilia are completely absent from the cochlear apex
• homozygotes exhibit rapid degeneration of cochlear hair cells during the second and third weeks of life
• cochlear HC degeneration is triggered by altered ionic permeability through the reticular lamina
• homozygotes display slower degeneration of cochlear IHCs, following rapid degeneration of OHCs
• by P18, IHCs are partially missing throughout the cochlea
• at >P7, homozygotes exhibit rapid loss of OHCs progressing from base to apex
• at P10-P13, OHCs are lost or disorganized throughout most of cochlear length, except for the extreme apex
• by P18, only a few OHCs with disorganized stereocilia are present at the most apical cochlear region
• OHC degeneration is first characterized by disorganization and loss of stereocilia, followed by swelling of cell bodies, shortening of cell length, submerging of cell bodies under the reticular lamina, and eventually death

behavior/neurological
N
• homozygotes exhibit no obvious behavioral abnormalities, such as circling, head tossing or hyperactivity (J:85071)
• no vestibular or motor dysfunction is detected, based on rotarod and elevated beam testing (J:85071)

Mouse Models of Human Disease
OMIM IDRef(s)
Deafness, Autosomal Recessive 29; DFNB29 614035 J:85071