Mouse Genome Informatics
hm
    Whrnwi/Whrnwi
involves: C57BL/6J * STOCK a Tyrp1b Myo5ad Oca2p Ednrbs
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
adipose tissue
• there is a noticeable deficiency of adipose tissue in the abdominal cavity

behavior/neurological
• at P9 to P10 when placed on their backs mutants take longer to return to an upright position
• some mutants at weaning age can swim if the head is not submerged
• adults can not swim
• mutants are restless and excitable
• at P14 to P16 the gait is unsteady and mutants constantly topple over
• this behavior is noticeable at P14 to P16 (J:269)
• this behavior is seen in adults (J:269)
• females tend to trample their young (J:269)

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

endocrine/exocrine glands
• 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)
• the seminal vesicle weight at 16 weeks in male mutants is significantly smaller (J:5538)
• the thymus weight at 3.5 and 18 months in female mutants is significantly lower

growth/size
• there is a noticeable deficiency of adipose tissue in the abdominal cavity
• 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)

hearing/vestibular/ear
• the specialized microvilli (stereocilia) that project from the apical surface of the inner and outer hair cells are abnormal
• from P5 up to P40, all IHCs along the entire length of the cochlea are similarly affected, with many abnormal stereocilia
• 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)
• 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
• 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)
• the number of outer hair cell stereocilia was sgnificantly reduced
• the center-to-center spacing between the stereocilia was greater
• at P80, both IHCs and OHCs are degenerating
• 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)
• 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)
• adults are deaf (J:269)
• adults are deaf (J:5037)

homeostasis/metabolism
• the blood glucose levels are significantly lower at 16 weeks in male mutants
• 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
• 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)
• liver glycogen and liver phosphorylase levels are significantly lower at 16 weeks in male mutants

immune system
• the thymus weight at 3.5 and 18 months in female mutants is significantly lower
• the white blood cell counts are significantly smaller at 15 weeks in male mutants

liver/biliary system
• the liver weight at 3.5 and 10 months in female mutants is significantly higher
• this difference is no longer significant at 18 months

renal/urinary system
• 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
• the seminal vesicle weight at 16 weeks in male mutants is significantly smaller (J:5538)
• the uterine weight at 3.5 months in female mutants is significantly smaller (J:5037)
• there is no significant difference at 10 and 18 months (J:5037)

nervous system
• the specialized microvilli (stereocilia) that project from the apical surface of the inner and outer hair cells are abnormal
• from P5 up to P40, all IHCs along the entire length of the cochlea are similarly affected, with many abnormal stereocilia
• 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)
• 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
• 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)
• the number of outer hair cell stereocilia was sgnificantly reduced
• the center-to-center spacing between the stereocilia was greater
• at P80, both IHCs and OHCs are degenerating
• 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)
• 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
• the thymus weight at 3.5 and 18 months in female mutants is significantly lower
• the white blood cell counts are significantly smaller at 15 weeks in male mutants

Mouse Models of Human Disease
OMIM IDRef(s)
Deafness, Autosomal Recessive 31; DFNB31 607084 J:269 , J:5037 , J:5538 , J:77939