Phenotypes Associated with This Genotype

Genotype
MGI:3712362

• Allelic Composition: Duox2^thyd/Duox2^thyd
• Genetic Background: B6(129)-Duox2^thyd/J

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

endocrine/exocrine glands

abnormal adenohypophysis morphology ( J:121821 )

• although the posterior and intermediate lobes of the pituitary appear normal, the anterior pituitary gland is dysplastic and has many large abnormal cells, some with multiple nuclei

abnormal thyroid follicle morphology ( J:121821 )

thyroid gland hyperplasia ( J:121821 )

• thyroid gland is highly dysplastic with few normal follicles and highly proliferating epithelial cells, which give rise to bilateral thyroid adenomas

decreased activity of thyroid gland ( J:121821 )

growth/size/body

decreased body size ( J:121821 )

• proportionally smaller than siblings

decreased body weight ( J:121821 )

• adults weigh approximately half that of littermate controls

hearing/vestibular/ear

delayed inner ear development ( J:121821 )

• at postnatal day 7 the epithelial cells that will form the inner sulcus of the organ of Corti are in a less-developed columnar form and still attached to a thickened tectorial membrane

• at postnatal day 14 the organ of Corti resembles that of the postnatal day 7 control, but by 8 weeks of age development of the organ of Corti has progressed to appear nearly normal but with a variably thickened tectorial membrane

abnormal tectorial membrane morphology ( J:121821 )

increased or absent threshold for auditory brainstem response ( J:121821 )

• ABR thresholds are on average 50-60 dB above those of heterozygous controls for all auditory test stimuli

homeostasis/metabolism

decreased circulating insulin-like growth factor I level ( J:121821 )

• at 8 weeks of age the average serum insulin-like growth factor level is 14.2 ng/ml versus 261 ng/ml in controls

increased circulating thyroid-stimulating hormone level ( J:121821 )

• at 8 weeks of age TSH levels are 100 to 1000 fold higher than in sex-matched heterozygotes

decreased circulating thyroxine level ( J:121821 )

• at 8 weeks of age serum T4 levels are 10-fold lower than in heterzygous controls in both males and females

nervous system

abnormal adenohypophysis morphology ( J:121821 )

• although the posterior and intermediate lobes of the pituitary appear normal, the anterior pituitary gland is dysplastic and has many large abnormal cells, some with multiple nuclei

reproductive system

infertility ( J:121821 )

• homozygotes do not breed

skeleton

skeleton phenotype ( J:121821 )

N • the growth plates appear normal

decreased bone mineral density ( J:121821 )

• DEXA analysis at 8 weeks of age reveals that total body bone mineral density is significantly reduced with no sex difference

decreased areal bone mineral density ( J:121821 )

• at 8 weeks of age, areal bone mineral density is significantly reduced with no sex difference

abnormal bone mineralization involved in bone maturation ( J:121821 )

• the whole skeleton appears under-mineralized with thin bones and narrow cortex

adipose tissue

decreased percent body fat/body weight ( J:121821 )

• DEXA analysis at 8 weeks of age shows decreased body fat relative to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital hypothyroidism		DOID:0050328	OMIM:PS275200	J:121821