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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tob1tm1Tya
targeted mutation 1, Tadashi Yamamoto
MGI:1933294
Summary 1 genotype
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Tob1tm1Tya/Tob1tm1Tya involves: 129S4/SvJae * C57BL/6 MGI:2655641


Genotype
MGI:2655641
hm1
Allelic
Composition
Tob1tm1Tya/Tob1tm1Tya
Genetic
Background
involves: 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tob1tm1Tya mutation (4 available); any Tob1 mutation (30 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
skeleton
• 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
• 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
• 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
• 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
• 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
• 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
• calvaria-derived cells from newborn homozygotes display exhibit enhanced BMP2-stimulated DNA synthesis relative to wild-type cells





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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
11/12/2024
MGI 6.24
The Jackson Laboratory