Phenotypes Associated with This Genotype

Genotype
MGI:3719582

• Allelic Composition: Thrb^tm1.1Syc/Thrb^tm1.1Syc
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * NIH Black Swiss

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

skeleton

short tibia ( J:103351 )

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

premature endochondral bone ossification ( J:103351 )

• E17.5 and P1 skeletons show advanced endochondral ossification and are larger than wild-type

premature intramembranous bone ossification ( J:103351 )

• advanced ossification of the skull

premature cranial suture closure ( J:103351 )

limbs/digits/tail

short tibia ( J:103351 )

• 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

abnormal cochlea morphology ( J:124153 )

• defects in cochlear morphogenesis become evident between P0/P1 and 3 weeks of age

abnormal organ of Corti morphology ( J:124153 )

• 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

cochlear hair cell degeneration ( J:124153 )

• 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

organ of Corti degeneration ( J:124153 )

• 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

abnormal tectorial membrane morphology ( J:124153 )

• at 6 weeks, the tectorial membrane is significantly thickened and shortened, possibly due to the membrane folding back upon itself

detached tectorial membrane ( J:124153 )

• at 6 weeks, the tectorial membrane does not appear to contact the organ of Corti in any turns of the cochlea

enlarged tectorial membrane ( J:124153 )

• 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

increased or absent threshold for auditory brainstem response ( J:124153 )

• 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

impaired hearing ( J:124153 )

• 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

cochlear hair cell degeneration ( J:124153 )

• 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		DO ID	OMIM ID(s)	Ref(s)
thyroid hormone resistance syndrome		DOID:11633	OMIM:188570 OMIM:274300	J:124153