Phenotypes Associated with This Genotype

Genotype
MGI:3036713

• Allelic Composition: Whrn^wi/Whrn^wi
• Genetic Background: involves: C57BL/6J * STOCK a Tyrp1^b Myo5a^d Oca2^p Ednrb^s

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

adipose tissue

decreased total body fat amount ( J:5538 )

• there is a noticeable deficiency of adipose tissue in the abdominal cavity

behavior/neurological

impaired righting response ( J:269 )

• at P9 to P10 when placed on their backs mutants take longer to return to an upright position

impaired swimming ( J:269 )

• some mutants at weaning age can swim if the head is not submerged

• adults can not swim

head bobbing ( J:269 , J:48657 )

• this behavior is noticeable at P14 to P16 (J:269)

head tossing ( J:269 , J:5037 )

• this behavior is seen in adults (J:269)

abnormal gait ( J:269 )

• at P14 to P16 the gait is unsteady and mutants constantly topple over

hyperactivity ( J:5037 )

• mutants are restless and excitable

circling ( J:269 , J:5037 , J:48657 )

abnormal maternal nurturing ( J:269 )

♀ • females tend to trample their young

cardiovascular system

increased heart weight ( J:5538 )

• the heart weight at 16 weeks in male mutants is significantly larger

endocrine/exocrine glands

enlarged adrenal glands ( J:5037 , J:5538 )

• the adrenal weight at 3.5, 10, and 18 months in female mutants is significantly higher (J:5037)

• the adrenal weight at 16 weeks in male mutants is significantly higher (J:5538)

decreased thymus weight ( J:5037 )

• the thymus weight at 3.5 and 18 months in female mutants is significantly lower

decreased seminal vesicle weight ( J:5538 )

♂ • the seminal vesicle weight at 16 weeks in male mutants is significantly smaller

growth/size/body

increased heart weight ( J:5538 )

• the heart weight at 16 weeks in male mutants is significantly larger

decreased body weight ( J:269 , J:5037 , J:5538 )

• at P9 to P10 and P14 to P16 mutants are smaller (J:269)

• the body weight at 3.5 and 18 months in female mutants is significantly lower (J:5037)

• the body weight at 13 to 16 weeks in male mutants is significantly lower (J:5538)

increased kidney weight ( J:5037 )

• the kidney weight at 3.5 and 10 months in female mutants is significantly higher

• this difference is no longer significant at 18 months

increased liver weight ( J:5037 )

• the liver weight at 3.5 and 10 months in female mutants is significantly higher

• this difference is no longer significant at 18 months

hearing/vestibular/ear

abnormal cochlear hair cell stereociliary bundle morphology ( J:77939 )

• the specialized microvilli (stereocilia) that project from the apical surface of the inner and outer hair cells are abnormal

abnormal cochlear inner hair cell morphology ( J:48657 )

• from P5 up to P40, all IHCs along the entire length of the cochlea are similarly affected, with many abnormal stereocilia

short inner hair cell stereocilia ( J:48657 , J:77939 , J:122600 )

• from P5 onwards, IHCs are abnormal with many short, stubby stereocilia, although the kinocilium is correctly positioned and of normal length (J:48657)

• overall the stereocilia of inner hair cells in mutants are significantly shorter at E18.5, P1, and P35 (J:77939)

• the length of stereocilia on inner hair cells in mutants decreases between P1 and P4 and between P4 and P35 rather than increasing (J:77939)

• the morphological differences between stereocilia in different ranks of inner hair cells are not as prominent in mutants at P35 (J:77939)

• however in mutants the stereocilia at the center of a rank are still significantly taller than those on the edge as is seen in controls (J:77939)

• stereocilia of inner hair cells are short with larger diameters without a corresponding increase in the number of actin filaments at P20 (J:122600)

abnormal cochlear outer hair cell morphology ( J:158897 )

• most outer hair cells exhibit a non-convex region on their apical circumference unlike wild-type cells

• outer hair cells exhibit a slight flattening of their neural sides compared to in wild-type mice

abnormal outer hair cell stereociliary bundle morphology ( J:48657 , J:77939 , J:122600 , J:158897 )

• at P5 (but not at P3), the center of the developing W-shape of OHC stereocilia still contains excess microvilli which have not yet been absorbed, indicating delayed development of OHC stereociliary bundles (J:48657)

• at P10, the extra OHC microvilli in the center of the W-shape have not yet cleared totally in the apical turn but have disappeared in the basal turn, while kinocilia are still present but regress by P15 (J:48657)

• outer hair cells appear normal until P4 (J:77939)

• on P4 the stereocilia are arranged in a U-shaped pattern rather than the normal W-shaped pattern (J:77939)

• in mutants on P15 and P35 stereocilia height within a rank of outer hair cells is irregular instead of uniform (J:77939)

• an increase in diameter and variable heights within bundles (J:122600)

• outer hair bundles exhibit a linear rather than V-shaped configuration unlike in wild-type mice (J:158897)

short outer hair cell stereocilia ( J:158897 )

decreased outer hair cell stereocilia number ( J:122600 )

• the number of outer hair cell stereocilia was sgnificantly reduced

• the center-to-center spacing between the stereocilia was greater

cochlear hair cell degeneration ( J:48657 )

• at P80, both IHCs and OHCs are degenerating

cochlear inner hair cell degeneration ( J:48657 , J:77939 )

• at P60, IHCs have still not degenerated or developed further; however, IHCs are degenerating at P80 (J:48657)

• by P80 both outer hair cells and inner hair cells in the base of the cochlear duct are degenerating (J:77939)

cochlear outer hair cell degeneration ( J:48657 , J:77939 )

• although apparently normal at P15, OHCs start showing signs of degeneration from P60 onwards (J:48657)

• by P60 outer hair cells are showing signs of degeneration (J:77939)

• by P80 both outer hair cells and inner hair cells in the base of the cochlear duct are degenerating (J:77939)

• by P80 only outer hair cells are degenerating in the apex of the cochlear duct (J:77939)

deafness ( J:269 , J:5037 , J:48657 )

• adults are deaf (J:269)

• adults are deaf (J:5037)

homeostasis/metabolism

decreased circulating glucose level ( J:5538 )

• the blood glucose levels are significantly lower at 16 weeks in male mutants

increased circulating corticosterone level ( J:5538 )

• consistent and significantly higher corticosterone levels in the plasma and adrenals

• corticosterone levels are higher in the adrenals when comparing per pair of adrenals or per 100 mg adrenals

increased oxygen consumption ( J:5037 , J:5538 )

• free and semi-restrained O₂ consumption is increased at 12 and 14 weeks and 14 months (J:5037)

• free and semi-restrained O₂ consumption is increased at 13 and 14 weeks respectively (J:5538)

decreased liver glycogen level ( J:5538 )

• liver glycogen and liver phosphorylase levels are significantly lower at 16 weeks in male mutants

immune system

decreased thymus weight ( J:5037 )

• the thymus weight at 3.5 and 18 months in female mutants is significantly lower

decreased leukocyte cell number ( J:5538 )

• the white blood cell counts are significantly smaller at 15 weeks in male mutants

liver/biliary system

increased liver weight ( J:5037 )

• the liver weight at 3.5 and 10 months in female mutants is significantly higher

• this difference is no longer significant at 18 months

decreased liver glycogen level ( J:5538 )

• liver glycogen and liver phosphorylase levels are significantly lower at 16 weeks in male mutants

renal/urinary system

increased kidney weight ( J:5037 )

• the kidney weight at 3.5 and 10 months in female mutants is significantly higher

• this difference is no longer significant at 18 months

reproductive system

decreased seminal vesicle weight ( J:5538 )

♂ • the seminal vesicle weight at 16 weeks in male mutants is significantly smaller

decreased uterus weight ( J:5037 )

♀ • the uterine weight at 3.5 months in female mutants is significantly smaller

♀ • there is no significant difference at 10 and 18 months

nervous system

abnormal cochlear hair cell stereociliary bundle morphology ( J:77939 )

• the specialized microvilli (stereocilia) that project from the apical surface of the inner and outer hair cells are abnormal

abnormal cochlear inner hair cell morphology ( J:48657 )

• from P5 up to P40, all IHCs along the entire length of the cochlea are similarly affected, with many abnormal stereocilia

short inner hair cell stereocilia ( J:48657 , J:77939 , J:122600 )

• from P5 onwards, IHCs are abnormal with many short, stubby stereocilia, although the kinocilium is correctly positioned and of normal length (J:48657)

• overall the stereocilia of inner hair cells in mutants are significantly shorter at E18.5, P1, and P35 (J:77939)

• the length of stereocilia on inner hair cells in mutants decreases between P1 and P4 and between P4 and P35 rather than increasing (J:77939)

• the morphological differences between stereocilia in different ranks of inner hair cells are not as prominent in mutants at P35 (J:77939)

• however in mutants the stereocilia at the center of a rank are still significantly taller than those on the edge as is seen in controls (J:77939)

• stereocilia of inner hair cells are short with larger diameters without a corresponding increase in the number of actin filaments at P20 (J:122600)

abnormal cochlear outer hair cell morphology ( J:158897 )

• most outer hair cells exhibit a non-convex region on their apical circumference unlike wild-type cells

• outer hair cells exhibit a slight flattening of their neural sides compared to in wild-type mice

abnormal outer hair cell stereociliary bundle morphology ( J:48657 , J:77939 , J:122600 , J:158897 )

• at P5 (but not at P3), the center of the developing W-shape of OHC stereocilia still contains excess microvilli which have not yet been absorbed, indicating delayed development of OHC stereociliary bundles (J:48657)

• at P10, the extra OHC microvilli in the center of the W-shape have not yet cleared totally in the apical turn but have disappeared in the basal turn, while kinocilia are still present but regress by P15 (J:48657)

• outer hair cells appear normal until P4 (J:77939)

• on P4 the stereocilia are arranged in a U-shaped pattern rather than the normal W-shaped pattern (J:77939)

• in mutants on P15 and P35 stereocilia height within a rank of outer hair cells is irregular instead of uniform (J:77939)

• an increase in diameter and variable heights within bundles (J:122600)

• outer hair bundles exhibit a linear rather than V-shaped configuration unlike in wild-type mice (J:158897)

short outer hair cell stereocilia ( J:158897 )

decreased outer hair cell stereocilia number ( J:122600 )

• the number of outer hair cell stereocilia was sgnificantly reduced

• the center-to-center spacing between the stereocilia was greater

cochlear hair cell degeneration ( J:48657 )

• at P80, both IHCs and OHCs are degenerating

cochlear inner hair cell degeneration ( J:48657 , J:77939 )

• at P60, IHCs have still not degenerated or developed further; however, IHCs are degenerating at P80 (J:48657)

• by P80 both outer hair cells and inner hair cells in the base of the cochlear duct are degenerating (J:77939)

cochlear outer hair cell degeneration ( J:48657 , J:77939 )

• although apparently normal at P15, OHCs start showing signs of degeneration from P60 onwards (J:48657)

• by P60 outer hair cells are showing signs of degeneration (J:77939)

• by P80 both outer hair cells and inner hair cells in the base of the cochlear duct are degenerating (J:77939)

• by P80 only outer hair cells are degenerating in the apex of the cochlear duct (J:77939)

hematopoietic system

decreased thymus weight ( J:5037 )

• the thymus weight at 3.5 and 18 months in female mutants is significantly lower

decreased leukocyte cell number ( J:5538 )

• the white blood cell counts are significantly smaller at 15 weeks in male mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive nonsyndromic deafness 31		DOID:0110490	OMIM:607084	J:269 , J:5037 , J:5538 , J:77939