Phenotypes Associated with This Genotype

Genotype
MGI:2676935

• Allelic Composition: Thrb^tm3Few/Thrb^tm3Few
• Genetic Background: involves: 129 * C57BL/6

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

endocrine/exocrine glands

increased thyrotroph cell number ( J:85158 )

• the number of anterior pituitary cells expressing the TSH-beta subunit is increased by 1.3 fold over control animals

enlarged thyroid gland ( J:85158 )

• an overall enlargement is observed

abnormal pituitary gland physiology ( J:85158 )

• after daily intraperitoneal supplementation with excess injected triiodothyronine (T₃) hormone, expression of serum TSH and TSH subunit mRNA levels were not suppressed, indicating severely compromised feedback regulation in the pituitary by thyroid hormone

increased activity of thyroid gland ( J:85158 )

homeostasis/metabolism

increased circulating thyroxine level ( J:85158 )

• total serum T₄ levels are increased 2-3 fold in homozygous mice

• free serum T₄ levels are elevated 2-fold in homozygous mice

increased circulating triiodothyronine level ( J:85158 )

• total serum T₃ levels are increased 2-3 fold in homozygous mice

increased circulating thyroid-stimulating hormone level ( J:85158 )

• basal serum thyroid-stimulating hormone levels are increased 20-fold compared to control animals, suggestive of central thyroid hormone resistance

vision/eye

abnormal retina cone cell morphology ( J:85158 )

• lack of M opsin (found in green cones)

• significantly increased levels of S opsin (found in blue cones) in the dorsal retina to levels roughly equivalent to ventral retina

• more uniform distribution of S opsin

hearing/vestibular/ear

abnormal cochlea morphology ( J:85158 )

cochlear outer hair cell degeneration ( J:85158 )

• in the basal third of the cochlea, scattered outer hair cell loss is seen; no region had less that 70% of the number found in controls

abnormal pillar cell morphology ( J:85158 )

• abnormalities in the position of the outer pillar feet are seen

enlarged tectorial membrane ( J:85158 )

• enlarged membrane with abnormal shape

increased or absent threshold for auditory brainstem response ( J:85158 )

• ABR threshold elevations of 20-30 dB over controls are seen at frequencies above ~10kHz

increased or absent distortion product otoacoustic emission threshold ( J:85158 )

• mildly elevated thresholds are seen at frequencies greater than ~10kHz, consistent with partial outer hair cell loss

sensorineural hearing loss ( J:85158 )

• threshold elevations of 20-30 dB at some frequencies

nervous system

increased thyrotroph cell number ( J:85158 )

• the number of anterior pituitary cells expressing the TSH-beta subunit is increased by 1.3 fold over control animals

abnormal pituitary gland physiology ( J:85158 )

• after daily intraperitoneal supplementation with excess injected triiodothyronine (T₃) hormone, expression of serum TSH and TSH subunit mRNA levels were not suppressed, indicating severely compromised feedback regulation in the pituitary by thyroid hormone

cochlear outer hair cell degeneration ( J:85158 )

• in the basal third of the cochlea, scattered outer hair cell loss is seen; no region had less that 70% of the number found in controls

abnormal retina cone cell morphology ( J:85158 )

• lack of M opsin (found in green cones)

• significantly increased levels of S opsin (found in blue cones) in the dorsal retina to levels roughly equivalent to ventral retina

• more uniform distribution of S opsin

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid hormone resistance syndrome		DOID:11633	OMIM:188570 OMIM:274300	J:85158