Phenotypes Associated with This Genotype

Genotype
MGI:2670876

hm1

• Allelic Composition: Thra^tm2Jas/Thra^tm2Jas
• Genetic Background: involves: 129

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

skeleton

skeleton phenotype ( J:120899 )

N • despite osteosclerosis in adult mice, bone mineralization is normal

abnormal osteoclast physiology ( J:120899 )

• at P154, the resorption surface is reduced 21% in cortical bone, and 9% in trabecular bone compared to in wild-type mice

short tibia ( J:120899 )

• up to 7% shorter between P21 and P56

abnormal long bone epiphyseal plate morphology ( J:120899 )

• wider with delayed secondary centers of ossification at P21, P56, and to a lesser extent at P154

• at P21, the reserve zone is enlarged while the hypertrophic zone is narrower than in wild-type mice

decreased width of hypertrophic chondrocyte zone ( J:120899 )

increased long bone epiphyseal plate size ( J:120899 )

• wide

abnormal bone structure ( J:120899 )

• at P21, calcified bone is decreased compared to in wild-type mice

decreased osteoclast cell number ( J:120899 )

• 13% at P154

decreased compact bone thickness ( J:120899 )

• 30% at P21

abnormal trabecular bone morphology ( J:120899 )

• in juvenile mice, the bone volume fraction and number of trabeculae are decreased compared to in wild-type mice

• at P154, trabecular bone mass is increased with increased connectivity and plate-like morphology compared to in wild-type mice

• trabecular bone volume fraction is increased 1.8-fold compared to in wild-type mice

increased trabecular bone thickness ( J:120899 )

• at P154

increased bone mass ( J:120899 )

osteosclerosis ( J:120899 )

• in adult mice

delayed endochondral bone ossification ( J:120899 )

abnormal chondrocyte physiology ( J:114970 )

• chondrocytes treated with T3 and/or BMP2 exhibit lower alkaline phosphatase activity compared with similarly treated wild-type cells

homeostasis/metabolism

decreased circulating thyroxine level ( J:68577 , J:120899 )

• at P56 but not P21 or P154 (J:120899)

decreased circulating insulin-like growth factor I level ( J:120899 )

• at P21

abnormal enzyme/coenzyme activity ( J:84537 )

• enterocytes show a moderate decrease in lactase and sucrase enzyme activity

abnormal response/metabolism to endogenous compounds ( J:120899 )

• at P154, mice exhibit thinning of trabecular bone volume fraction following treatment with T4 unlike similarly treated wild-type mice

cardiovascular system

decreased heart ventricle muscle contractility ( J:68577 )

• time to peak tension and time to 50% relaxation are prolonged compared to in wild-type mice

decreased heart rate ( J:68577 )

prolonged QRS complex duration ( J:68577 )

• QRS duration is increased compared to in wild-type mice

digestive/alimentary system

abnormal intestinal mucosa morphology ( J:84537 )

• decrease in thickness of the mucosa

abnormal intestinal goblet cell morphology ( J:84537 )

• decrease in the number of goblet cells in the ileum

decreased small intestinal villus height ( J:84537 )

• reduction in villus height that results from a decrease in the number of epithelial cells per crypt-villus axis

abnormal enterocyte physiology ( J:84537 )

• enterocytes show a moderate decrease in lactase and sucrase enzyme activity

abnormal enterocyte proliferation ( J:84537 )

• proliferation is impaired but apparently normal differentiation; number of proliferating epithelial cells per crypt is reduced in the distal small intestine

• administration of T3 to induce hyperthyroidism, does not stimulate proliferation of crypt cells as in wild-type, despite higher levels of serum T3

muscle

decreased heart ventricle muscle contractility ( J:68577 )

• time to peak tension and time to 50% relaxation are prolonged compared to in wild-type mice

endocrine/exocrine glands

decreased activity of thyroid gland ( J:120899 )

• mice exhibit skeletal hypothyrodism

growth/size/body

decreased body weight ( J:120899 )

• at P21, P56, and P70

postnatal growth retardation ( J:120899 )

• until P56

hematopoietic system

decreased osteoclast cell number ( J:120899 )

• 13% at P154

abnormal osteoclast physiology ( J:120899 )

• at P154, the resorption surface is reduced 21% in cortical bone, and 9% in trabecular bone compared to in wild-type mice

immune system

decreased osteoclast cell number ( J:120899 )

• 13% at P154

abnormal osteoclast physiology ( J:120899 )

• at P154, the resorption surface is reduced 21% in cortical bone, and 9% in trabecular bone compared to in wild-type mice

limbs/digits/tail

short tibia ( J:120899 )

• up to 7% shorter between P21 and P56

short limbs ( J:120899 )

• at P21

short tail ( J:120899 )

• up to 17% shorter between P21 and P56

cellular

abnormal intestinal goblet cell morphology ( J:84537 )

• decrease in the number of goblet cells in the ileum

abnormal enterocyte proliferation ( J:84537 )

• proliferation is impaired but apparently normal differentiation; number of proliferating epithelial cells per crypt is reduced in the distal small intestine

• administration of T3 to induce hyperthyroidism, does not stimulate proliferation of crypt cells as in wild-type, despite higher levels of serum T3