Phenotypes Associated with This Genotype

Genotype
MGI:3818484

• Allelic Composition: Tyrobp^tm1.1Viv/Tyrobp^tm1.1Viv
• Genetic Background: B6.129P2-Tyrobp^tm1.1Viv

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

nervous system

nervous system phenotype ( J:95232 )

N • despite the reduction in microglial cells, the number of astrocytes is normal

abnormal microglial cell morphology ( J:95232 )

• at P10 or P15, the number of microglial cell numbers are decreased compared to in wild-type mice

abnormal axon morphology ( J:95232 )

• axon diameters are increased compared to in wild-type mice

abnormal myelination ( J:95232 )

• mice exhibit defects in myelin distribution and hypomyelination in the frontal brain regions compared to wild-type mice

• however, mice exhibit no evidence of oligodendrocyte degeneration, inflammation, microvascular changes or major axonal alterations

abnormal excitatory postsynaptic currents ( J:96801 )

• the ratio of AMPA receptor excitatory postsynaptic current at -60 and +40 mV is increased compared to in wild-type mice

enhanced long-term potentiation ( J:96801 )

• mice exhibit an increased long term potentiation (LTP) with smaller decay compared to in wild-type mice without a difference in glutamate release probability at Schaffer collateral inputs

• mice exhibit a 3-fold increase in LTP and a 100% increase in NMDAR-independent LTP at Schaffer collateral synapses compared to wild-type mice

skeleton

increased bone mineral content ( J:95232 )

• bone mineral content is increased compared to wild-type mice

increased bone mineral density ( J:95232 )

• bone mineral density is increased compared to wild-type mice

increased trabecular bone volume ( J:95232 )

• trabecular bone volume is doubled compared to controls

increased bone trabecula number ( J:95232 )

• increase in trabecular numbers resulting in a decrease in trabecular separation

increased bone mass ( J:95232 , J:129304 )

• bone mass is increased 21% compared to in wild-type mice (J:129304)

osteopetrosis ( J:95232 )

• mild

abnormal bone ossification ( J:95232 )

• bone formation rates are reduced by more than 50% compared to in wild-type mice

• bone mineralizing surfaces are decreased compared to in wild-type mice

• however, mineral apposition rates are normal

abnormal bone remodeling ( J:95232 , J:129304 )

• mice exhibit reduced bone remodeling due to defects in bone resorption (J:95232)

• following ovariectamy, mice exhibit an increased bone loss compared to in similarly treated wild-type mice (J:129304)

abnormal osteoclast physiology ( J:95232 , J:129304 )

• osteoclast differentiation in vitro and function in vivo are impaired compared to in wild-type mice (J:95232)

• collagen type I degradation products are decreased compared to in wild-type mice (J:129304)

decreased bone resorption ( J:95232 , J:129304 )

• decreased levels of deoxypyridinoline indicates impaired osteoclast-mediated bone resorption compared to in wild-type mice (J:95232)

• however, TRAP activity indicates that osteoclast numbers are normal (J:95232)

• in vitro, restored osteoclast differentiation by the presence of lymphocytes does not result in restored bone resorption as do wild-type cells (J:129304)

immune system

abnormal myelopoiesis ( J:95232 )

• bone marrow cells are unable to generate multinucleated osteoclasts or microglial cells under specific conditions unlike wild-type bone marrow cells

• however, bone marrow cells can be induced to form dendritic cells and macrophages

abnormal microglial cell morphology ( J:95232 )

• at P10 or P15, the number of microglial cell numbers are decreased compared to in wild-type mice

abnormal osteoclast physiology ( J:95232 , J:129304 )

• osteoclast differentiation in vitro and function in vivo are impaired compared to in wild-type mice (J:95232)

• collagen type I degradation products are decreased compared to in wild-type mice (J:129304)

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:96801 )

• mice treated with ifenprodil exhibit increased depression of NMDAR currents compared to similarly treated wild-type mice

hematopoietic system

abnormal myelopoiesis ( J:95232 )

• bone marrow cells are unable to generate multinucleated osteoclasts or microglial cells under specific conditions unlike wild-type bone marrow cells

• however, bone marrow cells can be induced to form dendritic cells and macrophages

abnormal microglial cell morphology ( J:95232 )

• at P10 or P15, the number of microglial cell numbers are decreased compared to in wild-type mice

abnormal osteoclast physiology ( J:95232 , J:129304 )

• osteoclast differentiation in vitro and function in vivo are impaired compared to in wild-type mice (J:95232)

• collagen type I degradation products are decreased compared to in wild-type mice (J:129304)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Nasu-Hakola disease		DOID:0090112	OMIM:221770	J:95232