Phenotypes Associated with This Genotype

Genotype
MGI:3581208

• Allelic Composition: Tshr^hyt/Tshr^hyt
• Genetic Background: CBy.RF-Tshr^hyt/J

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

endocrine/exocrine glands

decreased activity of thyroid gland ( J:130062 )

• mice are hypothyroid

nervous system

decreased cochlear outer hair cell number ( J:110962 )

• some missing outer hair cells are noted

abnormal outer hair cell stereociliary bundle morphology ( J:110962 )

• many outer hair cells display a lack of mature appearing stereocilia; a contiguous membrane covers the apex of the ciliary bundles in mutants

decreased outer hair cell stereocilia number ( J:110962 )

decreased dopaminergic neuron number ( J:85902 )

• 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

abnormal organ of Corti morphology ( J:110962 )

• the tunnel is dysplastic with a very narrow opening whereas the space of Nuel is absent

decreased cochlear outer hair cell number ( J:110962 )

• some missing outer hair cells are noted

abnormal outer hair cell stereociliary bundle morphology ( J:110962 )

• many outer hair cells display a lack of mature appearing stereocilia; a contiguous membrane covers the apex of the ciliary bundles in mutants

decreased outer hair cell stereocilia number ( J:110962 )

abnormal tectorial membrane morphology ( J:110962 )

• 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

increased or absent threshold for auditory brainstem response ( J:110962 , J:111112 )

• 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)

decreased distortion product otoacoustic emission amplitude ( J:110962 )

• DPOAE amplitudes are significantly reduced in mutants

increased or absent distortion product otoacoustic emission threshold ( J:110962 )

• 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

deafness ( J:111112 )

• mutant mice remained profoundly deaf on P24

limbs/digits/tail

decreased femur compact bone thickness ( J:130062 )

• the ratio of femur length to cortical bone width is increased by 50%

short limbs ( J:130062 )

• limbs are 16% shorter

decreased bone mineral density of caudal vertebrae ( J:130062 )

• relative and cumulative frequencies of micromineralization densities are reduced in caudal vertebrae

skeleton

decreased bone mineral density of caudal vertebrae ( J:130062 )

• relative and cumulative frequencies of micromineralization densities are reduced in caudal vertebrae

decreased bone mineral density of femur ( J:130062 )

• femoral bone mineral density is reduced by 18%

decreased bone volume ( J:130062 )

• bone volume fraction is reduced by 22%

decreased compact bone thickness ( J:130062 )

• 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

decreased femur compact bone thickness ( J:130062 )

• the ratio of femur length to cortical bone width is increased by 50%

abnormal bone trabecula morphology ( J:130062 )

• long bones have abnormal trabecular architecture, with trabeculae being coarser, more plate-like and of increased connectivity

abnormal epiphyseal plate morphology ( J:130062 )

• wider growth plates due to widening of only the reserve zone and proliferative zone

abnormal long bone epiphyseal plate proliferative zone ( J:130062 )

• widening of the proliferative zone

abnormal bone mineralization ( J:130062 )

• mice exhibit reduced bone mineralization

delayed bone ossification ( J:130062 )

• mice exhibit delayed formation of secondary ossification centers

delayed endochondral bone ossification ( J:130062 )

• the proximal tibia epiphysis exhibits delayed and incomplete ossification and has disrupted growth plate architecture

abnormal bone remodeling ( J:130062 )

• presence of abnormally retained and highly mineralized calcified cartilage in trabeculae, indicating impaired trabecular remodeling

immune system

increased pro-B cell number ( J:111014 )

• 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

decreased B cell number ( J:111014 )

• mutants have a lower absolute number of B lineage cells

• mutant bone marrow B cells have reduced proliferative capacity than wild-type

hematopoietic system

increased pro-B cell number ( J:111014 )

• 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

decreased B cell number ( J:111014 )

• mutants have a lower absolute number of B lineage cells

• mutant bone marrow B cells have reduced proliferative capacity than wild-type

homeostasis/metabolism

impaired adaptive thermogenesis ( J:139995 )

decreased circulating progesterone level ( J:72929 )

♀ • females show low progesterone levels

increased thyroid-stimulating hormone level ( J:130062 )

• TSH levels are elevated 2300-fold

decreased thyroxine level ( J:130062 )

• T4 levels are reduced by 95%

reproductive system

decreased superovulation rate ( J:72929 )

♀ • a response to gonadotropin treatment is followed by a decrease in ovulation

absent estrous cycle ( J:72929 )

♀ • mature mutant females show continuous dioestrus

impaired luteinization ( J:72929 )

♀ • mutants show poor corpus luteum development

abnormal uterine environment ( J:72929 )

♀ • females show no implantation

behavior/neurological

circling ( J:85902 )

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

unidirectional circling ( J:85902 )

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

increased stereotypic behavior ( J:85902 )

• 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)

abnormal frequency of paradoxical sleep ( J:72929 )

growth/size/body

decreased body size ( J:85902 )

• 42% of offspring from matings of heterozygous females and homozygous males are small compared to littermates

decreased body weight ( J:85902 )

• homozygous mice have reduced body weight compared to wild-type littermates

decreased body length ( J:85902 )

• 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