Mouse Genome Informatics
hm
    Thrbtm1.1Syc/Thrbtm1.1Syc
involves: 129S6/SvEvTac * C57BL/6J * NIH Black Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
skeleton
• tibias are 11% shorter at 2 weeks of age and only 2% shorter at 4 weeks, indicating an accelerated growth spurt between these ages
• E17.5 and P1 skeletons show advanced endochondral ossification and are larger than wild-type
• advanced ossification of the skull

limbs/digits/tail
• tibias are 11% shorter at 2 weeks of age and only 2% shorter at 4 weeks, indicating an accelerated growth spurt between these ages

hearing/vestibular/ear
• defects in cochlear morphogenesis become evident between P0/P1 and 3 weeks of age
• at 6 weeks, neither the tunnel of Corti nor the space of Nuel appear to have opened though both inner and outer pillar cells are present in the middle cochlear turn
• at this age, inner and outer pillar cells are not easily recognizable and the fluid spaces are reduced in the basal turn
• at 6 weeks, homozygotes show a highly variable loss of cochlear hair cells ranging from a normal complement to almost complete degeneration in both apical and basal turns
• at 6 weeks, an almost complete degeneration of the organ of Corti is noted in the apical cochlear turn
• cells are present along the basilar membrane but no specific cell types are identified
• at 6 weeks, the tectorial membrane is significantly thickened and shortened, possibly due to the membrane folding back upon itself
• at 6 weeks, the tectorial membrane does not appear to contact the organ of Corti in any turns of the cochlea
• at 6 weeks, the tectorial membrane is enlarged throughout the cochlear duct; however, a consistent gradient in morphology is observed
• in the basal turn, the tectorial membrane displays the smallest degree of thickening but the highest degree of folding
• in the middle turn, the degree of membrane thickening is increased relative to the basal turn but the level of folding is slightly reduced
• in the apical turn, the highest degree of thickening is observed though the amount of folding is minimal
• at 3 and 6 weeks of age, homozygotes display significantly elevated ABR thresholds (72-98 dB SPL) in response to click, 8-, 16- and 32-kHz pure tone stimuli relative to wild-type (22-44 dB SPL) or heterozygous (23-43 dB SPL) littermates
• at 6 weeks of age, homozygotes display a severe to profound hearing loss at all test frequencies
• however, no circling, head tossing or other behaviors suggestive of vestibular dysfunction are observed

nervous system
• at 6 weeks, homozygotes show a highly variable loss of cochlear hair cells ranging from a normal complement to almost complete degeneration in both apical and basal turns

Mouse Models of Human Disease
OMIM IDRef(s)
Thyroid Hormone Resistance, Generalized, Autosomal Dominant; GRTH 188570 J:124153