Phenotypes Associated with This Genotype

Genotype
MGI:5897617

• Allelic Composition: Tg(TG-RET/CCDC6)42Cled/0
• Genetic Background: involves: FVB/N

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

growth/size/body

decreased body size ( J:93679 )

• dwarfism

• T4 supplementation corrects the dwarfism

endocrine/exocrine glands

increased thyrotroph cell number ( J:93679 )

• pituitary glands have marked hyperplasia of thyrotrophs

• 90% of cells in the pars distalis are thyrotrophs

increased thyrotroph cell size ( J:93679 )

• pituitary glands have marked hypertrophy of thyrotrophs

abnormal thyroid follicle morphology ( J:55883 )

• large and irregular thyroid follicles with little colloid are seen at E16.5 and at E18.5

• increase in proliferation rate of thyroid follicular cells at E16.5 and 2-3 weeks of age, although proliferation in the thyroid decreases with age

increased thyroid carcinoma incidence ( J:55883 , J:93679 )

• all mice exhibit bilateral thyroid tumors by 4 days of age (J:55883)

• thyroid tumors tend to arise from the central portions of the thyroid lobes with peripheral areas frequently containing irregular, dilated follicles (J:55883)

• administration of exogenous T4 delays thyroid tumor development (J:55883)

• all mice develop bilateral thyroid carcinomas similar to human papillary thyroid carcinomas as early as 1 month of age (J:93679)

• intrathryoidal and periglandulal invasion is seen in all mice (J:93679)

abnormal thyroid gland physiology ( J:55883 )

• pregnant dams intraperitoneally injected with radioiodide show reduced iodine concentrating activity of thyroid glands at E18

• radioiodide concentrating activity is reduced in the thyroid glands at all ages

• total iodide uptake activity in the thyroid glands is 30-fold lower than in controls

• mice supplemented with T4, when serum T4 and TSH levels are comparable to controls, total iodide uptake activity in the thyroid gland is 7-fold lower than in controls

decreased activity of thyroid gland ( J:55883 , J:93679 )

• congenital hypothyroidism in all mice (J:93679)

homeostasis/metabolism

decreased circulating thyroxine level ( J:93679 )

• low serum thyroxine (T4) levels

decreased circulating triiodothyronine level ( J:93679 )

• low serum triiodothyronine (T3) levels

increased thyroid-stimulating hormone level ( J:55883 )

increased circulating thyroid-stimulating hormone level ( J:93679 )

• high serum TSH levels

neoplasm

increased thyroid carcinoma incidence ( J:55883 , J:93679 )

• all mice exhibit bilateral thyroid tumors by 4 days of age (J:55883)

• thyroid tumors tend to arise from the central portions of the thyroid lobes with peripheral areas frequently containing irregular, dilated follicles (J:55883)

• administration of exogenous T4 delays thyroid tumor development (J:55883)

• all mice develop bilateral thyroid carcinomas similar to human papillary thyroid carcinomas as early as 1 month of age (J:93679)

• intrathryoidal and periglandulal invasion is seen in all mice (J:93679)

nervous system

increased thyrotroph cell number ( J:93679 )

• pituitary glands have marked hyperplasia of thyrotrophs

• 90% of cells in the pars distalis are thyrotrophs

increased thyrotroph cell size ( J:93679 )

• pituitary glands have marked hypertrophy of thyrotrophs

renal/urinary system

paraphimosis ( J:93679 )

♂ • males develop penile prolapse (paraphimosis) with edema and ulceration at about 45 days of age

reproductive system

paraphimosis ( J:93679 )

♂ • males develop penile prolapse (paraphimosis) with edema and ulceration at about 45 days of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
papillary thyroid carcinoma		DOID:3969	OMIM:188550	J:55883 , J:93679