Phenotypes associated with this allele

• Allele Symbol: Tshr^tm1Rmar
• Allele Name: targeted mutation 1, Russell Marians
• Allele ID: MGI:2447142
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tshr^tm1Rmar/Tshr^tm1Rmar	involves: 129S1/Sv	MGI:5779646
hm2	Tshr^tm1Rmar/Tshr^tm1Rmar	involves: 129S1/Sv * C57BL/6J	MGI:3766096
cn3	Braf^tm1Cpri/Braf^tm1Cpri Tshr^tm1Rmar/Tshr^tm1Rmar Tg(TPO-cre)1Shk/0	involves: 129P2/OlaHsd * 129S1/Sv * FVB/NCr	MGI:5779645

Genotype
MGI:5779646

hm1

• Allelic Composition: Tshr^tm1Rmar/Tshr^tm1Rmar
• Genetic Background: involves: 129S1/Sv

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

endocrine/exocrine glands

abnormal thyroid follicle morphology ( J:168249 )

• hypotrophic thyroid follicles

small thyroid gland ( J:168249 )

Genotype
MGI:3766096

hm2

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

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

Genotype
MGI:5779645

cn3

• Allelic Composition: Braf^tm1Cpri/Braf^tm1Cpri; Tshr^tm1Rmar/Tshr^tm1Rmar; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * FVB/NCr

endocrine/exocrine glands

abnormal thyroid follicle morphology ( J:168249 )

• architecture of thyroid follicles is disrupted at 3 weeks of age

increased thyroid tumor incidence ( J:168249 )

• mice develop low-grade papillary thyroid cancer by 9 weeks of age, however, tumors are smaller and lack the characteristic tall cell features and are less invasive than in single Braf^tm1Cpri conditional mice

small thyroid gland ( J:168249 )

neoplasm

increased thyroid tumor incidence ( J:168249 )

• mice develop low-grade papillary thyroid cancer by 9 weeks of age, however, tumors are smaller and lack the characteristic tall cell features and are less invasive than in single Braf^tm1Cpri conditional mice