Phenotypes associated with this allele

• Allele Symbol: Tyrobp^tm1.1Viv
• Allele Name: targeted mutation 1.1, Eric Vivier
• Allele ID: MGI:2386271
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tyrobp^tm1.1Viv/Tyrobp^tm1.1Viv	B6.129P2-Tyrobp^tm1.1Viv	MGI:3818484
hm2	Tyrobp^tm1.1Viv/Tyrobp^tm1.1Viv	involves: 129P2/OlaHsd * BALB/cJ * C57BL/6	MGI:3818477
hm3	Tyrobp^tm1.1Viv/Tyrobp^tm1.1Viv	involves: 129P2/OlaHsd * C57BL/6	MGI:3818418
cx4	Rag1^tm1Mom/Rag1^tm1Mom Tyrobp^tm1.1Viv/Tyrobp^tm1.1Viv	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * C57BL/10	MGI:3818486
cx5	Fcer1g^tm1Rav/Fcer1g^tm1Rav Tyrobp^tm1.1Viv/Tyrobp^tm1.1Viv	involves: 129P2/OlaHsd * C57BL/6	MGI:3818420

Genotype
MGI:3818484

hm1

• 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

Genotype
MGI:3818477

hm2

• Allelic Composition: Tyrobp^tm1.1Viv/Tyrobp^tm1.1Viv
• Genetic Background: involves: 129P2/OlaHsd * BALB/cJ * C57BL/6

immune system

increased dendritic cell number ( J:64764 )

• the number of CD11c+ dendritic cells is increased 2-fold in the intestinal lamina propria and dramatically increased in the subepithelial dome of the Peyer's patches compared to in wild-type mice

• the number of MHC class II+ cells with dendtritic morphology in the buccal mucosa and skin is increased compared to in wild-type mice

• however, the numbers of DEC205+ dendritic cells in the interfollicular T cell region, the accumulation of dendritic cells in the spleen and peripheral lymph nodes, and differentiation of dendrictic cells are normal

impaired natural killer cell mediated cytotoxicity ( J:64764 )

• NK cells exhibit severely impaired lysis of CHO cells and fail to lyse tumor target cells upon Ly49D antibody activations unlike wild-type NK cells

• natural cytoxicity of DX5+ splenocytes towards macrophage cell lines J774 and IC-21 is severely diminished compared to in wild-type cells

• however, natural cytotoxicity towards YAC-1, Bw15.02, RMA, and RMA/S cells and NK cell differentiation are normal

decreased susceptibility to type IV hypersensitivity reaction ( J:64764 )

• mice exhibit a severely impaired contact sensitivity response following exposure to 2,4-dinitrofluoro-benzene compared to similarly treated wild-type mice

hematopoietic system

increased dendritic cell number ( J:64764 )

• the number of CD11c+ dendritic cells is increased 2-fold in the intestinal lamina propria and dramatically increased in the subepithelial dome of the Peyer's patches compared to in wild-type mice

• the number of MHC class II+ cells with dendtritic morphology in the buccal mucosa and skin is increased compared to in wild-type mice

• however, the numbers of DEC205+ dendritic cells in the interfollicular T cell region, the accumulation of dendritic cells in the spleen and peripheral lymph nodes, and differentiation of dendrictic cells are normal

impaired natural killer cell mediated cytotoxicity ( J:64764 )

• NK cells exhibit severely impaired lysis of CHO cells and fail to lyse tumor target cells upon Ly49D antibody activations unlike wild-type NK cells

• natural cytoxicity of DX5+ splenocytes towards macrophage cell lines J774 and IC-21 is severely diminished compared to in wild-type cells

• however, natural cytotoxicity towards YAC-1, Bw15.02, RMA, and RMA/S cells and NK cell differentiation are normal

Genotype
MGI:3818418

hm3

• Allelic Composition: Tyrobp^tm1.1Viv/Tyrobp^tm1.1Viv
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

reproductive system

abnormal maternal decidual layer morphology ( J:100668 )

♀ • at E12, the mesometrial lymphoid aggregate of pregnancy is enlarged compared to in wild-type mice

abnormal decidua basalis morphology ( J:100668 )

♀ • at E10, the decidua basalis is larger compared to in wild-type mice but, by E12, the decidua basalis is reduced compared to in wild-type mice

decreased uterine NK cell number ( J:100668 )

♀ • at E10 in the decidua basalis

♀ • at E10 and E12 in the mesometrial lymphoid aggregate of pregnancy

abnormal uterine spiral artery morphology ( J:100668 )

♀ • at E12, the decidual spiral arterial vessel to lumen area is increased compared to in wild-type mice

failure of embryo implantation ( J:100668 )

♀ • embryo implantation sites are absent at E6 and E8

abnormal uterine spiral artery remodeling ( J:100668 )

♀ • at E12, thick-walled arteries are prominent in implantation site unlike in wild-type mice

♀ • uterine NK cells fail to modify the spiral arteries of the deciduas as in wild-type mice

reduced fertility ( J:100668 )

• fewer mice become pregnant following mating compared to wild-type mice

embryo

abnormal maternal decidual layer morphology ( J:100668 )

♀ • at E12, the mesometrial lymphoid aggregate of pregnancy is enlarged compared to in wild-type mice

abnormal decidua basalis morphology ( J:100668 )

♀ • at E10, the decidua basalis is larger compared to in wild-type mice but, by E12, the decidua basalis is reduced compared to in wild-type mice

decreased uterine NK cell number ( J:100668 )

♀ • at E10 in the decidua basalis

♀ • at E10 and E12 in the mesometrial lymphoid aggregate of pregnancy

abnormal uterine spiral artery morphology ( J:100668 )

♀ • at E12, the decidual spiral arterial vessel to lumen area is increased compared to in wild-type mice

enlarged placenta ( J:100668 )

• at E10 and E12

immune system

decreased uterine NK cell number ( J:100668 )

♀ • at E10 in the decidua basalis

♀ • at E10 and E12 in the mesometrial lymphoid aggregate of pregnancy

hematopoietic system

decreased uterine NK cell number ( J:100668 )

♀ • at E10 in the decidua basalis

♀ • at E10 and E12 in the mesometrial lymphoid aggregate of pregnancy

endocrine/exocrine glands

decreased uterine NK cell number ( J:100668 )

♀ • at E10 in the decidua basalis

♀ • at E10 and E12 in the mesometrial lymphoid aggregate of pregnancy

Genotype
MGI:3818486

cx4

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Tyrobp^tm1.1Viv/Tyrobp^tm1.1Viv
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * C57BL/10

skeleton

increased bone trabecula number ( J:129304 )

• the number of trabeculae are increased compared to wild-type mice

• however, trabecular thickness is normal

increased trabecular bone connectivity density ( J:129304 )

• the space between trabeculae is reduced compared to in wild-type mice

increased bone mass ( J:129304 )

• bone mass is increased 30% compared to in Tyrobp^tm1.1Viv homozygotes and 60% compared to in wild-type mice and Rag1^tm1Mom homozygotes

osteopetrosis ( J:129304 )

• severe

abnormal bone remodeling ( J:129304 )

• following ovariectamy, mice exhibit an increased bone loss compared to in similarly treated wild-type mice or Tyrobp^tm1.1Viv homozygotes

abnormal osteoclast physiology ( J:129304 )

• collagen type I degradation products are decreased 17% compared to in wild-type mice

immune system

abnormal osteoclast physiology ( J:129304 )

• collagen type I degradation products are decreased 17% compared to in wild-type mice

hematopoietic system

abnormal osteoclast physiology ( J:129304 )

• collagen type I degradation products are decreased 17% compared to in wild-type mice

Genotype
MGI:3818420

cx5

• Allelic Composition: Fcer1g^tm1Rav/Fcer1g^tm1Rav; Tyrobp^tm1.1Viv/Tyrobp^tm1.1Viv
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

reproductive system

abnormal maternal decidual layer morphology ( J:100668 )

♀ • at E12, the mesometrial lymphoid aggregate of pregnancy is smaller than in wild-type mice

abnormal decidua basalis morphology ( J:100668 )

♀ • at E10, the decidua basalis is reduced compared to in wild-type mice

decreased uterine NK cell number ( J:100668 )

♀ • at E10 in the deciduas basalis and at E12 in the mesometrial lymphoid aggregate of pregnancy

abnormal uterine spiral artery morphology ( J:100668 )

♀ • at E10 and E12, the decidual spiral arterial vessel to lumen area is increased compared to in wild-type mice

abnormal uterine spiral artery remodeling ( J:100668 )

♀ • at E12, thick-walled arteries are prominent in implantation site unlike in wild-type mice

♀ • uterine NK cells fail to modify the spiral arteries of the deciduas as in wild-type mice

reduced fertility ( J:100668 )

• fewer mice of one line become pregnant following mating compared to wild-type mice

• midgestational (E10) fetal loss is greater than in wild-type mice

• however, mice derived from a different line exhibit normal pregnancy rates

embryo

abnormal maternal decidual layer morphology ( J:100668 )

♀ • at E12, the mesometrial lymphoid aggregate of pregnancy is smaller than in wild-type mice

abnormal decidua basalis morphology ( J:100668 )

♀ • at E10, the decidua basalis is reduced compared to in wild-type mice

decreased uterine NK cell number ( J:100668 )

♀ • at E10 in the deciduas basalis and at E12 in the mesometrial lymphoid aggregate of pregnancy

abnormal uterine spiral artery morphology ( J:100668 )

♀ • at E10 and E12, the decidual spiral arterial vessel to lumen area is increased compared to in wild-type mice

small placenta ( J:100668 )

• at E10 and E12

immune system

decreased uterine NK cell number ( J:100668 )

♀ • at E10 in the deciduas basalis and at E12 in the mesometrial lymphoid aggregate of pregnancy

decreased interferon-gamma secretion ( J:100668 )

• at E6 through E14 in the mesometrial triangle, mesometrial lymphoid aggregate of pregnancy and deciduas basalis

hematopoietic system

decreased uterine NK cell number ( J:100668 )

♀ • at E10 in the deciduas basalis and at E12 in the mesometrial lymphoid aggregate of pregnancy

endocrine/exocrine glands

decreased uterine NK cell number ( J:100668 )

♀ • at E10 in the deciduas basalis and at E12 in the mesometrial lymphoid aggregate of pregnancy