Phenotypes Associated with This Genotype

Genotype
MGI:3766096

• Allelic Composition: Tshr^tm1Rmar/Tshr^tm1Rmar
• Genetic Background: involves: 129S1/Sv * C57BL/6J

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

mortality/aging

lethality at weaning, complete penetrance ( J:80513 )

• die within 1 week of weaning unless fed a diet supplemented with thyroid powder

• mutants can also survive when the preweaning period is extended to P28

growth/size/body

postnatal growth retardation ( J:80513 )

• developmental and growth delays

homeostasis/metabolism

increased circulating thyroid-stimulating hormone level ( J:80513 )

• untreated mutants and mutants rescued by prolonged weaning and maintained on a normal diet exhibit elevated TSH levels

abnormal thyroid hormone level ( J:80513 )

decreased circulating levels of thyroid hormone ( J:80513 )

• hypothyroid with no detectable thyroid hormone, however when mutants are fed normal diet with a high dose thyroid supplement, they become hyperthyroid and TSH levels are suppressed, indicating that the normal feedback mechanism regulating thyroid hormone secretion remains intact

decreased circulating thyroxine level ( J:80513 )

• mutants rescued by prolonged weaning and maintained on a normal diet exhibit low serum T4 levels

decreased circulating triiodothyronine level ( J:80513 )

• mutants rescued by prolonged weaning and maintained on a normal diet exhibit low serum T3 levels

endocrine/exocrine glands

abnormal thyroid follicle morphology ( J:80513 )

• thyroids have fewer follicles and more non-follicle associated cells within the gland than in wild-type

small thyroid gland ( J:80513 )

• thyroids are about 50% of the size of normal thyroids

abnormal thyroid gland physiology ( J:80513 )

• mutants fail to release thyroid hormone into the circulation in response to exogenous TSH

decreased activity of thyroid gland ( J:80513 )

• hypothyroid with no detectable thyroid hormone and elevated TSH, however when placed on thyroid hormone replacement therapy from weaning, mutants become euthyroid

• mutants rescued by prolonged weaning and maintained on a normal diet are severely hypothyroid as indicated by low serum T4 and T3 levels and elevated TSH levels

iodide oxidation defect ( J:80513 )

• thyroid glands produce uniodinated thyroglobulin, but the ability to concentrate and organify iodide can be restored to thyroids when cultured in the presence of the adenylate cyclase agonist forskolin

reproductive system

reduced fertility ( J:80513 )

• mutants that survive due to prolonged preweaning period do not reproduce, however mutants supplemented with thyroid powder are fertile

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital hypothyroidism		DOID:0050328	OMIM:PS275200	J:80513