Phenotypes associated with this allele

• Allele Symbol: Tob1^tm1Tya
• Allele Name: targeted mutation 1, Tadashi Yamamoto
• Allele ID: MGI:1933294
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tob1^tm1Tya/Tob1^tm1Tya	involves: 129S4/SvJae * C57BL/6	MGI:2655641

Genotype
MGI:2655641

hm1

• Allelic Composition: Tob1^tm1Tya/Tob1^tm1Tya
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

skeleton

abnormal osteoblast differentiation ( J:66504 )

• ex vivo, calvaria-derived cultures containing osteoblast precursors and/or immature osteoblasts of newborn homozygotes show a significant increase in the number of alkaline-phosphate (ALP)-positive cells, suggesting that osteoblast differentiation is enhanced

• upon exposure to rhBMP2, the ALP activity of mutant calvaria-derived cells is significantly increased relative to similarly-derived wild-type cells

• although ALP activity remains at background levels by day 7 of culture at at low concentrations of rhBMP2, it is significantly increased by week 3 of culture even without exogenous BMP2

increased osteoblast cell number ( J:66504 )

• at 4 and 9 months of age, the osteoblast surface (an index of osteoblast population) in mutant trabecular bone is 250% greater than that of wild-type littermates

• in contrast, no differences are observed in osteoclast and eroded surface, indicating that increased bone mass is not due to decreased osteoclast numbers or impaired osteoclast function

increased bone mass ( J:66504 )

• at 2 months but not at 2 weeks of age, homozygotes display a bone mass that is ~130% that of control littermates, as revealed by X-ray computer tomography

• however, serum levels of major bone metabolizing hormones and factors remain normal

increased trabecular bone mass ( J:66504 )

• histologic analysis of undecalcified sections of mutant tibia shows a significant increase in trabecular bone at 9 months of age

• the bone volume/total tissue volume (BV/TV), a histomorphometric index of trabecular bone mass, is increased to 140% and 250% of that in control littermates at 4 and 9 months of age, respectively

abnormal bone ossification ( J:66504 )

• at 4 and 9 months of age, homozygotes display an accelerated rate of long bone (tibia) formation, as indicated by double-labeling analysis with calcein (a marker of newly formed bone)

• following daily injections of rhBMP2 onto the center of neonatal parietal bones for 7 days, homozygotes display increased orthotopic (new) bone formation, with a ~2-fold increase in mean calvaria thickness relative to wild-type mice

cellular

abnormal osteoblast differentiation ( J:66504 )

• ex vivo, calvaria-derived cultures containing osteoblast precursors and/or immature osteoblasts of newborn homozygotes show a significant increase in the number of alkaline-phosphate (ALP)-positive cells, suggesting that osteoblast differentiation is enhanced

• upon exposure to rhBMP2, the ALP activity of mutant calvaria-derived cells is significantly increased relative to similarly-derived wild-type cells

• although ALP activity remains at background levels by day 7 of culture at at low concentrations of rhBMP2, it is significantly increased by week 3 of culture even without exogenous BMP2

increased cell proliferation ( J:66504 )

• calvaria-derived cells from newborn homozygotes display exhibit enhanced BMP2-stimulated DNA synthesis relative to wild-type cells