Analysis Tools
endocrine/exocrine glands
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• mice are hypothyroid
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nervous system
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• some missing outer hair cells are noted
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• many outer hair cells display a lack of mature appearing stereocilia; a contiguous membrane covers the apex of the ciliary bundles in mutants
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• circling mice have ~40% fewer dopaminergic neurons in the midbrain than wild-type or heterozygotes
• circling animals appear to have fewer dopaminergic neurons on the left side
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hearing/vestibular/ear
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• the tunnel is dysplastic with a very narrow opening whereas the space of Nuel is absent
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• some missing outer hair cells are noted
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• many outer hair cells display a lack of mature appearing stereocilia; a contiguous membrane covers the apex of the ciliary bundles in mutants
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• in some mutants, the tectorial membrane is shortened and distorted while in others, the membrane is connected to the inner sulcus cells by a fibrillate band
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• auditory brainstem response thresholds show significantly elevated mean thresholds (left ear 84.4 dB, right ear 83.9) compared to wild-type (left ear 47.9 dB and 47.5dB)
(J:110962)
• although thresholds improved by approximately 30 dB by P60, residual frequency-dependent deficits of 20-70 dB were observed
(J:111112)
• rate of threshold improvement in mutant mice was approximately ten times slower than in normal mice
(J:111112)
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• DPOAE amplitudes are significantly reduced in mutants
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• homozygotes display an increased distortion product otoacoustic emission (DPOAE) threshold
• detection thresholds measured at DPOAE frequencies of 8-18 kHz are significantly higher in mutants than wild-type
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limbs/digits/tail
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• the ratio of femur length to cortical bone width is increased by 50%
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short limbs
(
J:130062
)
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• limbs are 16% shorter
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• relative and cumulative frequencies of micromineralization densities are reduced in caudal vertebrae
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skeleton
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• relative and cumulative frequencies of micromineralization densities are reduced in caudal vertebrae
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• femoral bone mineral density is reduced by 18%
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• bone volume fraction is reduced by 22%
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• long bones have reduced cortical thickness and mid-diaphysis cortical bone thickness is reduced by 26%
• the ratio of the diameter between endosteal cortical bone surfaces to the diameter between periosteal surfaces is increased
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• the ratio of femur length to cortical bone width is increased by 50%
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• long bones have abnormal trabecular architecture, with trabeculae being coarser, more plate-like and of increased connectivity
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• wider growth plates due to widening of only the reserve zone and proliferative zone
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• widening of the proliferative zone
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• mice exhibit reduced bone mineralization
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• mice exhibit delayed formation of secondary ossification centers
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• the proximal tibia epiphysis exhibits delayed and incomplete ossification and has disrupted growth plate architecture
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• presence of abnormally retained and highly mineralized calcified cartilage in trabeculae, indicating impaired trabecular remodeling
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immune system
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• pro-B cells from mutant bone marrow show a reduced proliferative capacity
• thyroxine treated animals show an increase in the number of cycing pro-B cells paralleled by an increase in the total number of pro-B cells
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• mutants have a lower absolute number of B lineage cells
• mutant bone marrow B cells have reduced proliferative capacity than wild-type
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hematopoietic system
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• pro-B cells from mutant bone marrow show a reduced proliferative capacity
• thyroxine treated animals show an increase in the number of cycing pro-B cells paralleled by an increase in the total number of pro-B cells
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• mutants have a lower absolute number of B lineage cells
• mutant bone marrow B cells have reduced proliferative capacity than wild-type
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homeostasis/metabolism
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• T4 levels are reduced by 95%
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• females show low progesterone levels
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• TSH levels are elevated 2300-fold
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reproductive system
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• a response to gonadotropin treatment is followed by a decrease in ovulation
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• mature mutant females show continuous dioestrus
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• mutants show poor corpus luteum development
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• females show no implantation
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behavior/neurological
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• all mice show a strong directional preference (93-100%)
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• mutants can walk in a straight line but when faced with a choice of turning one way or the other always turn in the same direction (same direction as circling behavior)
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growth/size/body
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• 42% of offspring from matings of heterozygous females and homozygous males are small compared to littermates
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• homozygous mice have reduced body weight compared to wild-type littermates
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• body length of homozygotes is less than littermates
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| congenital hypothyroidism | DOID:0050328 |
OMIM:PS275200 |
J:110962 , J:130062 | |
