Phenotypes associated with this allele

• Allele Symbol: Tyrobp^tm1Ttk
• Allele Name: targeted mutation 1, Toshiyuki Takai
• Allele ID: MGI:2450834
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tyrobp^tm1Ttk/Tyrobp^tm1Ttk	B6.129P2-Tyrobp^tm1Ttk	MGI:5296506
hm2	Tyrobp^tm1Ttk/Tyrobp^tm1Ttk	involves: 129P2/OlaHsd * C57BL/6	MGI:2450846
cx3	Oscar^tm1Ywc/Oscar^tm1Ywc Tyrobp^tm1Ttk/Tyrobp^tm1Ttk	involves: 129P2/OlaHsd * C57BL/6	MGI:5301435

Genotype
MGI:5296506

hm1

• Allelic Composition: Tyrobp^tm1Ttk/Tyrobp^tm1Ttk
• Genetic Background: B6.129P2-Tyrobp^tm1Ttk

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

immune system

increased B cell proliferation ( J:177613 )

• in response to with anti-BCR monoclonal antibody (anti-IgM mAb), LPS (a TLR-4 ligand), or CpG (a TLR-9 ligand) stimulation

increased germinal center B cell number ( J:177613 )

• increased frequencies following NP-CG or NP-Ficoll immunization

increased spleen germinal center number ( J:177613 )

• following NP-Ficoll immunization

increased spleen germinal center size ( J:177613 )

• following NP-CG immunization

increased IgG2a level ( J:177613 )

• following NP-CG immunization

increased IgG3 level ( J:177613 )

• following NP-Ficoll immunization

increased interleukin-6 secretion ( J:177613 )

• from B cells stimulated with CpG

increased autoantibody level ( J:177613 )

• against cardiolipin, double-strand DNA, and histone

increased anti-double stranded DNA antibody level ( J:177613 )

hematopoietic system

increased B cell proliferation ( J:177613 )

• in response to with anti-BCR monoclonal antibody (anti-IgM mAb), LPS (a TLR-4 ligand), or CpG (a TLR-9 ligand) stimulation

increased germinal center B cell number ( J:177613 )

• increased frequencies following NP-CG or NP-Ficoll immunization

increased spleen germinal center number ( J:177613 )

• following NP-Ficoll immunization

increased spleen germinal center size ( J:177613 )

• following NP-CG immunization

increased IgG2a level ( J:177613 )

• following NP-CG immunization

increased IgG3 level ( J:177613 )

• following NP-Ficoll immunization

cellular

increased B cell proliferation ( J:177613 )

• in response to with anti-BCR monoclonal antibody (anti-IgM mAb), LPS (a TLR-4 ligand), or CpG (a TLR-9 ligand) stimulation

Genotype
MGI:2450846

hm2

• Allelic Composition: Tyrobp^tm1Ttk/Tyrobp^tm1Ttk
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

Osteopetrosis in Tyrobp^tm1Ttk/Tyrobp^tm1Ttk mice

limbs/digits/tail

increased bone mineral density of caudal vertebrae ( J:81823 )

skeleton

abnormal osteoclast morphology ( J:81823 )

• 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

abnormal osteoclast physiology ( J:81823 )

• in vitro, mutant osteoclasts had a significantly reduced ability to form resorptive pits on the dentin surface, while control osteoclasts made many pits

increased bone mineral density ( J:81823 )

• slight increase is seen at 12 weeks of age, most notably in the tail bones and the metaphyseal regions of the femurs

increased bone mineral density of caudal vertebrae ( J:81823 )

increased bone mineral density of femur ( J:81823 )

increased trabecular bone mass ( J:81823 )

• 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

osteopetrosis ( J:81823 )

• the increase in trabecular bone amount is progressive with age

nervous system

abnormal oligodendrocyte morphology ( J:81823 )

• ectopic immature oligodendrocytes are found in the fimbria and internal capsule, adjacent to the thalamus at 1.5 and 3 months of age

abnormal neuron morphology ( J:81823 )

• in the medial thalamus of 6 month old mice, degenerated synapses and accumulated synaptic vesicles are seen

abnormal axon morphology ( J:81823 )

• the cross-sectional shapes of unmyelinated axons are slightly distorted compared with those of myelinated axons

abnormal myelination ( J:81823 )

• 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

reduced sensorimotor gating ( J:81823 )

abnormal inhibitory postsynaptic currents ( J:81823 )

• mice exhibit an impairment in the developmental changes of the decay time constant in GABAergic mIPSCs

decreased prepulse inhibition ( J:81823 )

• significantly reduced prepulse inhibition is seen in homozygous mice

behavior/neurological

behavior/neurological phenotype ( J:81823 )

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

decreased startle reflex ( J:81823 )

• mice show reduced response to acoustic stimuli

hematopoietic system

abnormal osteoclast morphology ( J:81823 )

• 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

abnormal osteoclast physiology ( J:81823 )

• 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

abnormal osteoclast morphology ( J:81823 )

• 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

abnormal osteoclast physiology ( J:81823 )

• in vitro, mutant osteoclasts had a significantly reduced ability to form resorptive pits on the dentin surface, while control osteoclasts made many pits

abnormal dendritic cell physiology ( J:110786 )

• cultured dendritic cells show reduced responses to Sema6D stimulation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Nasu-Hakola disease		DOID:0090112	OMIM:221770	J:81823

Genotype
MGI:5301435

cx3

• Allelic Composition: Oscar^tm1Ywc/Oscar^tm1Ywc; Tyrobp^tm1Ttk/Tyrobp^tm1Ttk
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

skeleton

skeleton phenotype ( J:178250 )

N • mice exhibit normal osteoblast parameters

abnormal osteoclast morphology ( J:178250 )

• mice exhibit decreased osteoclast number and size compared with Tyrobp^tm1Ttk homozygotes

abnormal osteoclast differentiation ( J:178250 )

• TGFB1-treated bone marrow macrophage immobilized on a minimal hOSCAR-binding triple-helical peptide (OSC^pep) fail to exhibit an increate in giant TRAP+ osteoclasts unlike similarly treated cells from Tyrobp^tm1Ttk homozygotes

decreased osteoclast cell number ( J:178250 )

• compared with Tyrobp^tm1Ttk homozygotes

abnormal osteoclast physiology ( J:178250 )

• mice exhibit a reduction in eroded bone surface compared with Tyrobp^tm1Ttk homozygotes

abnormal trabecular bone morphology ( J:178250 )

• mice exhibit increased bone trabecula number, increased trabecular bone volume, and decreased trabecular space compared with Tyrobp^tm1Ttk homozygotes

increased trabecular bone volume ( J:178250 )

• compared with Tyrobp^tm1Ttk homozygotes

increased bone trabecula number ( J:178250 )

• compared with Tyrobp^tm1Ttk homozygotes

cellular

abnormal osteoclast differentiation ( J:178250 )

• TGFB1-treated bone marrow macrophage immobilized on a minimal hOSCAR-binding triple-helical peptide (OSC^pep) fail to exhibit an increate in giant TRAP+ osteoclasts unlike similarly treated cells from Tyrobp^tm1Ttk homozygotes

hematopoietic system

abnormal osteoclast morphology ( J:178250 )

• mice exhibit decreased osteoclast number and size compared with Tyrobp^tm1Ttk homozygotes

abnormal osteoclast differentiation ( J:178250 )

• TGFB1-treated bone marrow macrophage immobilized on a minimal hOSCAR-binding triple-helical peptide (OSC^pep) fail to exhibit an increate in giant TRAP+ osteoclasts unlike similarly treated cells from Tyrobp^tm1Ttk homozygotes

decreased osteoclast cell number ( J:178250 )

• compared with Tyrobp^tm1Ttk homozygotes

abnormal osteoclast physiology ( J:178250 )

• mice exhibit a reduction in eroded bone surface compared with Tyrobp^tm1Ttk homozygotes

immune system

abnormal osteoclast morphology ( J:178250 )

• mice exhibit decreased osteoclast number and size compared with Tyrobp^tm1Ttk homozygotes

abnormal osteoclast differentiation ( J:178250 )

• TGFB1-treated bone marrow macrophage immobilized on a minimal hOSCAR-binding triple-helical peptide (OSC^pep) fail to exhibit an increate in giant TRAP+ osteoclasts unlike similarly treated cells from Tyrobp^tm1Ttk homozygotes

decreased osteoclast cell number ( J:178250 )

• compared with Tyrobp^tm1Ttk homozygotes

abnormal osteoclast physiology ( J:178250 )

• mice exhibit a reduction in eroded bone surface compared with Tyrobp^tm1Ttk homozygotes