Mouse Genome Informatics
hm1
    Myo7a4626SB/Myo7a4626SB
involves: 129S7/SvEvBrd * BALB/cRl * C3H * C57BL/6J * CBA/Ca
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• stereocilia of the lateral rows are longer than in complimented mice (Hprt1tm3Brd/Hprt1+ Myo7a4626SB/ Myo7a4626SB)
• however, treatment with cytochalasin decreases the difference between stereocilia length

nervous system
• stereocilia of the lateral rows are longer than in complimented mice (Hprt1tm3Brd/Hprt1+ Myo7a4626SB/ Myo7a4626SB)
• however, treatment with cytochalasin decreases the difference between stereocilia length


Mouse Genome Informatics
hm2
    Myo7a4626SB/Myo7a4626SB
involves: BALB/cRl
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• lateral links that connect stereocilia to each other are sparse and frequently disrupted
• ankle links are not present in P5 mice
• E17.5 embryos have disorganized and fragmented inner hair cell (IHC) stereociliary bundles
• stereociliary generally assemble into two to three clumps at the cell apical surface instead of forming single V-shaped bundles
• kinocillia show large mean deviations from the plane cell polarity axis (PCP) with only 36% of the kinocillia being within 15 degrees of the PCP compared to 84% in wild-type mice
• the mean absolute kinociliary deviation is 26 degrees compared to 8 degrees in wild-type mice
• at P5, outer hair cell fold angle peaks at zero degrees indicating no detectable concavity unlike in wild-type mice
• the contour of the cuticular plate remains convex unlike in wild-type mice
• outer hair cells exhibit a slight flattening of their neural and abneural sides compared to in wild-type mice
• E18.5 embryos have disorganized and fragmented outer hair cell (OHC) stereociliary bundles (J:135991)
• stereociliary generally assemble into two to three clumps at the cell apical surface instead of forming single V-shaped bundles (J:135991)
• bundles are fragmented compared to in wild-type mice (J:158897)
• starting at P5 the short and medium rows of the stereocillia start regressing and dissappear by P15
• many stereocillia of the small and medium rows in P0 mice are shorter than expected and do not elongate further

nervous system
• lateral links that connect stereocilia to each other are sparse and frequently disrupted
• ankle links are not present in P5 mice
• E17.5 embryos have disorganized and fragmented inner hair cell (IHC) stereociliary bundles
• stereociliary generally assemble into two to three clumps at the cell apical surface instead of forming single V-shaped bundles
• kinocillia show large mean deviations from the plane cell polarity axis (PCP) with only 36% of the kinocillia being within 15 degrees of the PCP compared to 84% in wild-type mice
• the mean absolute kinociliary deviation is 26 degrees compared to 8 degrees in wild-type mice
• at P5, outer hair cell fold angle peaks at zero degrees indicating no detectable concavity unlike in wild-type mice
• the contour of the cuticular plate remains convex unlike in wild-type mice
• outer hair cells exhibit a slight flattening of their neural and abneural sides compared to in wild-type mice
• E18.5 embryos have disorganized and fragmented outer hair cell (OHC) stereociliary bundles (J:135991)
• stereociliary generally assemble into two to three clumps at the cell apical surface instead of forming single V-shaped bundles (J:135991)
• bundles are fragmented compared to in wild-type mice (J:158897)
• starting at P5 the short and medium rows of the stereocillia start regressing and dissappear by P15
• many stereocillia of the small and medium rows in P0 mice are shorter than expected and do not elongate further


Mouse Genome Informatics
hm3
    Myo7a4626SB/Myo7a4626SB
involves: BALB/cRl * 47BS/Rl * C3Hf/Rl * C57BL/10Rl * CBA/Ca
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• disorganized compared to control, similar to homozygous Cdh23v
• the apical surface of stereocilia on OHCs show indentations unlike homozygous Cdh23v

nervous system
• disorganized compared to control, similar to homozygous Cdh23v
• the apical surface of stereocilia on OHCs show indentations unlike homozygous Cdh23v


Mouse Genome Informatics
ht4
    Myo7a4626SB/Myo7a+
involves: BALB/cRl * 47BS/Rl * CBA/Ca
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• number is lower in all three rows in region centered at 14% of total cochlear duct length at 11-12 weeks of age; innermost row is most severely affected
• at the 33% region (30 kHz) of the coclear duct, numbers of outer hair cells in rows 1 and 2 are significantly reduced
• after 2 hours exposure to noise (8-16 kHz, 103 dB SPL), no hair cell loss at 14% or 33% regions, or at 58% region relative to non-exposed animals despite considerable threshold shift of 35 dB (at 12 kHz)
• stereocilia exhibit damage at 58% region following noise exposure; in noise-exposed animals, gaps in ranks of stereocilia are observed
• splayed stereocilia leaning outward from the bundle so that tips are not in contact with adjacent row are seen; number (percent of total) of splayed cilia per rank is increased >8-fold with noise exposure
• significant reduction in number of stereocilia per rank is seen in noise-exposed mice compared to non-exposed animals
• compound action potential (CAP) thresholds are significantly raised compared to wild-type mice at low (3, 6, and 9 kHz) and high (18, 24, and 30 kHz) frequencies at 11-12 weeks of age
• elevated CAP thresholds indicate hearing loss

nervous system
• number is lower in all three rows in region centered at 14% of total cochlear duct length at 11-12 weeks of age; innermost row is most severely affected
• at the 33% region (30 kHz) of the coclear duct, numbers of outer hair cells in rows 1 and 2 are significantly reduced
• after 2 hours exposure to noise (8-16 kHz, 103 dB SPL), no hair cell loss at 14% or 33% regions, or at 58% region relative to non-exposed animals despite considerable threshold shift of 35 dB (at 12 kHz)
• stereocilia exhibit damage at 58% region following noise exposure; in noise-exposed animals, gaps in ranks of stereocilia are observed
• splayed stereocilia leaning outward from the bundle so that tips are not in contact with adjacent row are seen; number (percent of total) of splayed cilia per rank is increased >8-fold with noise exposure
• significant reduction in number of stereocilia per rank is seen in noise-exposed mice compared to non-exposed animals
• compound action potential (CAP) thresholds are significantly raised compared to wild-type mice at low (3, 6, and 9 kHz) and high (18, 24, and 30 kHz) frequencies at 11-12 weeks of age


Mouse Genome Informatics
ht5
    Myo7aHdb/Myo7a4626SB
involves: BALB/c * 47BS/Rl * C3HeB/FeJ * CBA/Ca
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Cochlear hair cell abnormalities in Myo7aHdb/Myo7a+, Myo7aHdb/Myo7a+ Myo7a4626SB/Myo7a+, and Myo7ash1/Myo7ash1 mice

hearing/vestibular/ear
• apical stereocilia bundles of inner hair cells appeared more disorganized than in Hdb heterozygotes but less than in Hdb homozygotes
• inner hair cell fusion was significantly reduced compared to that seen in Hdb homozygotes but not when compared to Hdb heterozygotes
• apical stereocilia bundles of outer hair cells appeared more disorganized than in Hdb heterozygotes but less than in Hdb homozygotes

nervous system
• apical stereocilia bundles of inner hair cells appeared more disorganized than in Hdb heterozygotes but less than in Hdb homozygotes
• inner hair cell fusion was significantly reduced compared to that seen in Hdb homozygotes but not when compared to Hdb heterozygotes
• apical stereocilia bundles of outer hair cells appeared more disorganized than in Hdb heterozygotes but less than in Hdb homozygotes

Mouse Models of Human Disease
OMIM IDRef(s)
Usher Syndrome, Type I; USH1 276900 J:93998


Mouse Genome Informatics
cx6
    Hprttm2Brd/Hprt+
Myo7a4626SB/Myo7a4626SB

involves: 129S7/SvEvBrd * BALB/cRl * C3H * C57BL/6J * CBA/Ca
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
N
• mice do not exhibit circling or head bobbing and have normal hair cells (J:132633)


Mouse Genome Informatics
cx7
    Hprttm3Brd/Hprt+
Myo7a4626SB/Myo7a4626SB

involves: 129S7/SvEvBrd * BALB/cRl * C3H * C57BL/6J * CBA/Ca
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
N
• mice do not exhibit circling or head bobbing and have normal hair cells (J:132633)


Mouse Genome Informatics
cx8
    Cdh23v/Cdh23v
Myo7a4626SB/Myo7a4626SB

involves: 47BS/Rl * CBA/Ca
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
N
• no histological abnormalities are seen and no evidence of photoreceptor cell loss is detected (J:109546)
• at 100-130 days of age, electroretinography analysis shows that double homozygous mice exhibit an attenuation of a- and b-wave amplitudes; however, this attenuation is not significantly different from the single homozygous mutant


Mouse Genome Informatics
cx9
    Cdh23v/Cdh23+
Myo7a4626SB/Myo7a+

involves: BALB/cRl * 47BS/Rl * CBA/Ca
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• stereocilia exhibit damage at 58% region following noise exposure; in noise-exposed animals, gaps in ranks of stereocilia are observed
• splayed stereocilia leaning outward from the bundle so that tips are not in contact with adjacent row are seen; number (percent of total) of splayed cilia per rank is increased >8-fold with noise exposure
• significant reduction in number of stereocilia per rank is seen in noise-exposed mice compared to non-exposed animals
• after 2 hours exposure to noise, CAP thresholds are not elevated at 12 kHz (frequency at center of bandwidth used) compared to non noise-exposed littermates; Cdh23sv heterozygotes and Cdh23;Myo7a double heterozygotes show significantly higher CAP threshold shifts compared to wild-type after noise exposure
• thresholds at 30 kHz are raised at in Cdh23 heterozygotes and wild-type, but not in Myo7a heterozygotes or double heterozygotes, although these mice already have significant (35 dB) hearing loss at this frequency

nervous system
• stereocilia exhibit damage at 58% region following noise exposure; in noise-exposed animals, gaps in ranks of stereocilia are observed
• splayed stereocilia leaning outward from the bundle so that tips are not in contact with adjacent row are seen; number (percent of total) of splayed cilia per rank is increased >8-fold with noise exposure
• significant reduction in number of stereocilia per rank is seen in noise-exposed mice compared to non-exposed animals
• after 2 hours exposure to noise, CAP thresholds are not elevated at 12 kHz (frequency at center of bandwidth used) compared to non noise-exposed littermates; Cdh23sv heterozygotes and Cdh23;Myo7a double heterozygotes show significantly higher CAP threshold shifts compared to wild-type after noise exposure
• thresholds at 30 kHz are raised at in Cdh23 heterozygotes and wild-type, but not in Myo7a heterozygotes or double heterozygotes, although these mice already have significant (35 dB) hearing loss at this frequency


Mouse Genome Informatics
cx10
    Cdh23v/Cdh23v
Myo7a4626SB/Myo7a+

mixed
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear

nervous system


Mouse Genome Informatics
cx11
    Cdh23v/Cdh23+
Myo7a4626SB/Myo7a4626SB

mixed
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• identical to Myo7a4626SB/ Myo7a4626SB

nervous system
• identical to Myo7a4626SB/ Myo7a4626SB


Mouse Genome Informatics
cx12
    Cdh23v/Cdh23v
Myo7a4626SB/Myo7a4626SB

mixed
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• identical to Myo7a4626SB/ Myo7a4626SB

nervous system
• identical to Myo7a4626SB/ Myo7a4626SB


Mouse Genome Informatics
cx13
    Cdh23v/Cdh23+
Myo7a4626SB/Myo7a+

mixed
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• similar to Cdh23v heterozygous mice
• although statistically not significant, there was a greater tendency for mice to lose their Preyer reflex if they carried both a Cdh23 and Myo7a mutation

behavior/neurological
• similar to Cdh23v heterozygous mice
• although statistically not significant, there was a greater tendency for mice to lose their Preyer reflex if they carried both a Cdh23 and Myo7a mutation


Mouse Genome Informatics
cx14
    Cdh23v-2J/Cdh23+
Myo7a4626SB/Myo7a+

mixed
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• similar to Cdh23v-2J heterozygous mice
• although statistically not significant, there was a greater tendency for mice to lose their Preyer reflex if they carried both a Cdh23 and Myo7a mutation

behavior/neurological
• similar to Cdh23v-2J heterozygous mice
• although statistically not significant, there was a greater tendency for mice to lose their Preyer reflex if they carried both a Cdh23 and Myo7a mutation