Phenotypes associated with this allele

• Allele Symbol: Whrn^wi
• Allele Name: whirler
• Allele ID: MGI:1857090
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Whrn^wi/Whrn^wi	involves: C57BL/6J * STOCK a Tyrp1^b Myo5a^d Oca2^p Ednrb^s	MGI:3036713
hm2	Whrn^wi/Whrn^wi	involves: STOCK a Tyrp1^b Myo5a^d Oca2^p Ednrb^s	MGI:3810337
ht3	Whrn^wi/Whrn^+	involves: C57BL/6J * STOCK a Tyrp1^b Myo5a^d Oca2^p Ednrb^s	MGI:3036723
cx4	Rpe65^450L/Rpe65^450L Whrn^wi/Whrn^wi	129.Cg(B6)-Whrn^wi	MGI:5572940

Genotype
MGI:3036713

hm1

• 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

Genotype
MGI:3810337

hm2

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

behavior/neurological

impaired righting response ( J:235390 )

• when placed on their backs, adult mice take several seconds to right themselves

head bobbing ( J:235390 )

circling ( J:235390 )

hearing/vestibular/ear

abnormal outer hair cell stereociliary bundle morphology ( J:235390 )

• at P21, OHC stereocilia bundles appear rounded (U- rather than W-shaped) and show irregular spacing between stereocilia rows relative to controls

short cochlear hair cell stereocilia ( J:132633 )

• hair cell stereocilia are shorter than in wild-type mice

short inner hair cell stereocilia ( J:235390 )

• at P21, IHC stereocilia are abnormally short

short vestibular hair cell stereocilia ( J:235390 )

• at P21, vestibular stereocilia are consistently shorter than in controls across all hair cells

• the length of tallest stereocilia in both the extrastriolar and striolar regions is reduced by ~80% relative to controls

absent cochlear microphonics ( J:235390 )

• at P13-P20, cochlear microphonics responses are below detection limits, within the noise floor

increased or absent threshold for auditory brainstem response ( J:235390 )

• at P20 and P98, mice fail to show any auditory brainstem response (ABR) to the highest sound stimulus used

abnormal auditory summating potential ( J:235390 )

• at P13-P20, summating potentials are detected in 27 of 28 mice studied, albeit at high stimulus intensities, suggesting that some hair cells can depolarize in response to sound

absent cochlear nerve compound action potential ( J:235390 )

• at P20, mice exhibit no compound action potentials (CAPs) even at the highest stimulus intensities used

deafness ( J:235390 )

• adult mice are profoundly deaf

nervous system

abnormal outer hair cell stereociliary bundle morphology ( J:235390 )

• at P21, OHC stereocilia bundles appear rounded (U- rather than W-shaped) and show irregular spacing between stereocilia rows relative to controls

short cochlear hair cell stereocilia ( J:132633 )

• hair cell stereocilia are shorter than in wild-type mice

short inner hair cell stereocilia ( J:235390 )

• at P21, IHC stereocilia are abnormally short

short vestibular hair cell stereocilia ( J:235390 )

• at P21, vestibular stereocilia are consistently shorter than in controls across all hair cells

• the length of tallest stereocilia in both the extrastriolar and striolar regions is reduced by ~80% relative to controls

absent cochlear microphonics ( J:235390 )

• at P13-P20, cochlear microphonics responses are below detection limits, within the noise floor

absent cochlear nerve compound action potential ( J:235390 )

• at P20, mice exhibit no compound action potentials (CAPs) even at the highest stimulus intensities used

Genotype
MGI:3036723

ht3

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

hearing/vestibular/ear

abnormal cochlear inner hair cell morphology ( J:77939 )

short inner hair cell stereocilia ( J:77939 )

• the stereocilia of inner hair cells in heterozygotes are slightly shorter at P35

• by P80 no hair cells are degenerating in the cochlear duct of heterozygotes unlike in homozygotes

nervous system

abnormal cochlear inner hair cell morphology ( J:77939 )

short inner hair cell stereocilia ( J:77939 )

• the stereocilia of inner hair cells in heterozygotes are slightly shorter at P35

• by P80 no hair cells are degenerating in the cochlear duct of heterozygotes unlike in homozygotes

Genotype
MGI:5572940

cx4

• Allelic Composition: Rpe65^450L/Rpe65^450L; Whrn^wi/Whrn^wi
• Genetic Background: 129.Cg(B6)-Whrn^wi

nervous system

abnormal retina rod cell inner segment morphology ( J:210386 )

• rhodopsin is mislocalized in rod inner segments

retina photoreceptor degeneration ( J:210386 )

• mice are more susceptible to continuous moderate light exposure induced photoreceptor degeneration than controls, showing on average a 25% reduction in the number of photoreceptors after a 6 day moderate 2500 lux light exposure

• mice reared under a 1500 lux light/dark cycle develop severe photoreceptor degeneration

• however, mice do not develop retinal degeneration when reared under normal conditions

• mice exposed to one hour 2000 lux light and then dark adapted for another 7 hours in repeated cycles for 2 weeks exhibit severe photoreceptor degeneration, to a similar extent that is seen with continuous (6 day) light exposure

vision/eye

abnormal retina rod cell inner segment morphology ( J:210386 )

• rhodopsin is mislocalized in rod inner segments

retina photoreceptor degeneration ( J:210386 )

• mice are more susceptible to continuous moderate light exposure induced photoreceptor degeneration than controls, showing on average a 25% reduction in the number of photoreceptors after a 6 day moderate 2500 lux light exposure

• mice reared under a 1500 lux light/dark cycle develop severe photoreceptor degeneration

• however, mice do not develop retinal degeneration when reared under normal conditions

• mice exposed to one hour 2000 lux light and then dark adapted for another 7 hours in repeated cycles for 2 weeks exhibit severe photoreceptor degeneration, to a similar extent that is seen with continuous (6 day) light exposure

abnormal eye physiology ( J:210386 )

• photoreceptors show delayed light-activated rod transducing translocation and its activation threshold is shifted to a higher level

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Usher syndrome type 2D		DOID:0110840	OMIM:611383	J:210386