Mouse Genome Informatics
hm
    Tyrobptm1Ttk/Tyrobptm1Ttk
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Osteopetrosis in Tyrobptm1Ttk/Tyrobptm1Ttk mice

skeleton
• osteoclasts apperar smaller than controls, but comparable numbers of multinucleated TRAP+ osteoclasts per unit trabecular area are seen in femurs of 6-week-old mutant and control mice
• however, in vitro studies show that the induction of multinucleated, TRAP+ osteoclasts was significantly hampered compared to controls
• in vitro, mutant osteoclasts were devoid of an actin ring, which is characteristic of mature and functional osteoclasts and is necessary for tight adhesion of osteoclasts to bone matrix
• in vitro, mutant osteoclasts had a significantly reduced ability to form resorptive pits on the dentin surface, while control osteoclasts made many pits
• slight increase is seen at 12 weeks of age, most notably in the tail bones and the metaphyseal regions of the femurs
• micro-CT scans show an increase in trabecular bone mass in the tibia at 40 weeks of age
• at 6 weeks of age, a significant increase in trabecular bone mass is seen compared to controls, but this difference is not seen at 3 weeks of age
• the increase in trabecular bone amount is progressive with age

nervous system
• ectopic immature oligodendrocytes are found in the fimbria and internal capsule, adjacent to the thalamus at 1.5 and 3 months of age
• in the medial thalamus of 6 month old mice, degenerated synapses and accumulated synaptic vesicles are seen
• the cross-sectional shapes of unmyelinated axons are slightly distorted compared with those of myelinated axons
• reduced expression of myelin basic protein in the thalamus at 1.5 and 3 months of age; this reduction is more severe in the frontal thalamus than in the posterior region
• in 6 month old mice, the number of myelinated axons in the medial thalamus is reduced, and many axons are unmyelinated
• mice exhibit an impairment in the developmental changes of the decay time constant in GABAergic mIPSCs
• significantly reduced prepulse inhibition is seen in homozygous mice

behavior/neurological
N
• at 3.5 months of age, analysis of motor function, nociceptive responses, and learning, including an electric shock test, a hot plate test, and a Morris water maze task indicated no differences compared to controls (J:81823)
• mice show reduced response to acoustic stimuli

hematopoietic system
• osteoclasts apperar smaller than controls, but comparable numbers of multinucleated TRAP+ osteoclasts per unit trabecular area are seen in femurs of 6-week-old mutant and control mice
• however, in vitro studies show that the induction of multinucleated, TRAP+ osteoclasts was significantly hampered compared to controls
• in vitro, mutant osteoclasts were devoid of an actin ring, which is characteristic of mature and functional osteoclasts and is necessary for tight adhesion of osteoclasts to bone matrix
• in vitro, mutant osteoclasts had a significantly reduced ability to form resorptive pits on the dentin surface, while control osteoclasts made many pits

immune system
• osteoclasts apperar smaller than controls, but comparable numbers of multinucleated TRAP+ osteoclasts per unit trabecular area are seen in femurs of 6-week-old mutant and control mice
• however, in vitro studies show that the induction of multinucleated, TRAP+ osteoclasts was significantly hampered compared to controls
• in vitro, mutant osteoclasts were devoid of an actin ring, which is characteristic of mature and functional osteoclasts and is necessary for tight adhesion of osteoclasts to bone matrix
• in vitro, mutant osteoclasts had a significantly reduced ability to form resorptive pits on the dentin surface, while control osteoclasts made many pits
• cultured dendritic cells show reduced responses to Sema6D stimulation

Mouse Models of Human Disease
OMIM IDRef(s)
Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy; 221770 J:81823