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Phenotypes Associated with This Genotype
Genotype
MGI:3581208
Allelic
Composition
Tshrhyt/Tshrhyt
Genetic
Background
CBy.RF-Tshrhyt/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tshrhyt mutation (1 available); any Tshr mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• mice are hypothyroid

nervous system
• some missing outer hair cells are noted
• many outer hair cells display a lack of mature appearing stereocilia; a contiguous membrane covers the apex of the ciliary bundles in mutants
• 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

hearing/vestibular/ear
• the tunnel is dysplastic with a very narrow opening whereas the space of Nuel is absent
• some missing outer hair cells are noted
• many outer hair cells display a lack of mature appearing stereocilia; a contiguous membrane covers the apex of the ciliary bundles in mutants
• 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
• 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)
• 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
• DPOAE amplitudes are significantly reduced in mutants
• mutant mice remained profoundly deaf on P24

limbs/digits/tail
• the ratio of femur length to cortical bone width is increased by 50%
• limbs are 16% shorter

skeleton
• relative and cumulative frequencies of micromineralization densities are reduced in caudal vertebrae
• femoral bone mineral density is reduced by 18%
• bone volume fraction is reduced by 22%
• 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
• the ratio of femur length to cortical bone width is increased by 50%
• long bones have abnormal trabecular architecture, with trabeculae being coarser, more plate-like and of increased connectivity
• wider growth plates due to widening of only the reserve zone and proliferative zone
• widening of the proliferative zone
• mice exhibit reduced bone mineralization
• mice exhibit delayed formation of secondary ossification centers
• the proximal tibia epiphysis exhibits delayed and incomplete ossification and has disrupted growth plate architecture
• presence of abnormally retained and highly mineralized calcified cartilage in trabeculae, indicating impaired trabecular remodeling

immune system
• 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
• mutants have a lower absolute number of B lineage cells
• mutant bone marrow B cells have reduced proliferative capacity than wild-type

hematopoietic system
• 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
• mutants have a lower absolute number of B lineage cells
• mutant bone marrow B cells have reduced proliferative capacity than wild-type

homeostasis/metabolism
• females show low progesterone levels
• TSH levels are elevated 2300-fold
• T4 levels are reduced by 95%

reproductive system
• a response to gonadotropin treatment is followed by a decrease in ovulation
• mature mutant females show continuous dioestrus
• females show no implantation
• mutants show poor corpus luteum development

behavior/neurological
• all mice show a strong directional preference (93-100%)
• all mice show a strong directional preference (93-100%)
• 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)

growth/size/body
• 42% of offspring from matings of heterozygous females and homozygous males are small compared to littermates
• homozygous mice have reduced body weight compared to wild-type littermates
• body length of homozygotes is less than littermates

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
congenital hypothyroidism DOID:0050328 OMIM:PS275200
J:110962 , J:130062


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
08/04/2020
MGI 6.15
The Jackson Laboratory