Phenotypes Associated with This Genotype

Genotype
MGI:2449164

• Allelic Composition: Myo7a^sh1/Myo7a^sh1
• Genetic Background: involves: BALB

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

Cochlear hair cell abnormalities in Myo7a^Hdb/Myo7a⁺, Myo7a^Hdb/Myo7a⁺ Myo7a^4626SB/Myo7a⁺, and Myo7a^sh1/Myo7a^sh1 mice

behavior/neurological

abnormal behavior ( J:15554 )

• when placed on a cold concrete floor mice rarely travel more than 6 feet and this distance is covered in short jerky stops and starts

increased fluid intake ( J:15554 )

• water consumption is increased compared to in wild-type mice

increased food intake ( J:15554 )

increased anxiety-related response ( J:15554 )

absent pinna reflex ( J:14858 )

• by 22 days

impaired swimming ( J:13130 )

• while mice can swim at a young age their lose their ability to do so in the second month of age

jerky movement ( J:15554 )

• mice display a nervous head movement characterized by rapid, successive jerking of the head upwards accompanied by sniffing and twitching of the vibrissae

• however, mice can cease their head jerking for periods of time and appear normal

head tossing ( J:93998 )

hyperactivity ( J:15554 , J:93998 )

circling ( J:15554 , J:93998 )

• 14% of mice exhibit a moderate circling behavior with a tendency to circle counter-clockwise (J:15554)

growth/size/body

slow postnatal weight gain ( J:15554 )

hearing/vestibular/ear

abnormal organ of Corti morphology ( J:14846 , J:28477 )

• formation of fluid spaces is delayed with no tunnel spaces evident until day 12 and intercellular spaces between hair cells not apparent until day 21 (J:14846)

• maturation of the organ of Corti is delayed as indicated by the presence of round or ovoid shaped outer hair cells at day 10 and deformation of Nuel's spaces and the tunnel of Corti (J:28477)

• by day 18 Nuel's spaces have not formed and the tectorial membrane remains attached to the reticular lamina (J:28477)

abnormal cochlear hair cell morphology ( J:14846 )

• the intercellular spaces that appear between hair cells occur at day 21 instead of day 10 as in wild-type mice

• efferent nerve innervation does not occur until day 12 compared to day 10 in wild-type mice and only a small number can be found

• mitochondrial swelling and vesicle formation are observed in both afferent and efferent nerve endings as mice age

• no auditory hair cells can be found between the level of the reticular lamina and the tectorial membrane

abnormal cochlear OHC efferent innervation pattern ( J:28477 )

• efferent arrival at the outer hair cell is delayed

• however, efferent nerve supply to the inner hair cells is normal if not over-abundant

cochlear hair cell degeneration ( J:13130 , J:14858 , J:93998 )

• degeneration of the hair cells occurs at 7 weeks of age (J:13130)

• by 4 months (J:14858)

stria vascularis degeneration ( J:14858 )

• by 4 months, the stria vascularis is atrophic

vestibular saccular macula degeneration ( J:13130 )

• at 21 days

abnormal ear physiology ( J:14858 )

• cochlear potential is delayed by one day compared to in wild-type mice and mice do not respond to the full range of frequencies

• eighth nerve activity N1 and N2 is delayed and never obtain the amplitude that they do in wild-type mice

• by day 22, eighth nerve action potential has disappeared

deafness ( J:14858 , J:15554 , J:93998 )

• by 22 days hearing is lost (J:14858)

• mice become deaf at around 22 to 30 days (J:15554)

reproductive system

reduced male fertility ( J:15554 )

♂ • males tend towards infertility because of their nervous condition

nervous system

abnormal cochlear hair cell morphology ( J:14846 )

• the intercellular spaces that appear between hair cells occur at day 21 instead of day 10 as in wild-type mice

• efferent nerve innervation does not occur until day 12 compared to day 10 in wild-type mice and only a small number can be found

• mitochondrial swelling and vesicle formation are observed in both afferent and efferent nerve endings as mice age

• no auditory hair cells can be found between the level of the reticular lamina and the tectorial membrane

abnormal cochlear OHC efferent innervation pattern ( J:28477 )

• efferent arrival at the outer hair cell is delayed

• however, efferent nerve supply to the inner hair cells is normal if not over-abundant

cochlear hair cell degeneration ( J:13130 , J:14858 , J:93998 )

• degeneration of the hair cells occurs at 7 weeks of age (J:13130)

• by 4 months (J:14858)

gliosis ( J:14891 )

• mice exhibit increases fibrous astrocytes in the medial vestibular nucleus

cochlear ganglion degeneration ( J:13130 , J:14846 , J:14858 , J:28477 )

• after 2 months (J:13130)

• spiral ganglia formation is delayed and fewer spiral ganglia are present (J:14846)

• at 22 days, mice have few spiral ganglia that are irregular, small, show more chromatic stiplings and minimal vascuolization (J:14858)

• by 4 months, ganglion cells have atrophied (J:14858)

• by day 10, spiral ganglion cells are unmyelinated and contain a large number of swollen mitochondria, dense bodies and an expanse of smooth endoplasmic reticulum (J:28477)

vestibular ganglion hypoplasia ( J:13130 )

• at 67 days

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Usher syndrome type 1		DOID:0110826	OMIM:276900	J:5133 , J:15554