Phenotypes associated with this allele

• Allele Symbol: Sh3bp2^tm1Bjro
• Allele Name: targeted mutation 1, Bjorn R Olsen
• Allele ID: MGI:3698401
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro	involves: 129S4/SvJae * BALB/cJ * C57BL/6J	MGI:3699094
ht2	Sh3bp2^tm1Bjro/Sh3bp2^+	involves: 129S4/SvJae * BALB/cJ * C57BL/6J	MGI:3699095
cn3	Nfatc1^tm3Glm/Nfatc1^tm3Glm Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro Tg(Mx1-cre)1Cgn/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:3831754
cx4	Rag1^tm1Mom/Rag1^tm1Mom Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro	involves: 129S4/SvJae * 129S7/SvEvBrd * BALB/cJ * C57BL/6J	MGI:3699096
cx5	Csf1^op/Csf1^op Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro	involves: 129S4/SvJae * BALB/cJ * C57BL/6J	MGI:3699098
cx6	Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro Tnf^tm1Gkl/Tnf^tm1Gkl	involves: 129S/SvEv * 129S4/SvJae * BALB/cJ * C57BL/6J	MGI:3699099

Genotype
MGI:3699094

hm1

• Allelic Composition: Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro
• Genetic Background: involves: 129S4/SvJae * BALB/cJ * C57BL/6J

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

growth/size/body

alveolar process atrophy ( J:117880 )

• loss of bone around teeth is seen at 10 weeks of age

mortality/aging

premature death ( J:117880 )

• impaired survival with age with only about 28% of homozygotes surviving to 30 weeks of age

skeleton

abnormal craniofacial bone morphology ( J:117880 )

abnormal neurocranium morphology ( J:117880 )

• reduced bone volume is seen at 10 weeks of age

abnormal jaw morphology ( J:117880 )

• reduced cortical bone thickness is seen at 10 weeks of age

• jaws display increased numbers of osteoclasts at 10 weeks of age

alveolar process atrophy ( J:117880 )

• loss of bone around teeth is seen at 10 weeks of age

abnormal long bone morphology ( J:117880 )

• bone loss is detected in the long bones

abnormal bone structure ( J:117880 )

abnormal osteoclast differentiation ( J:117880 )

• bone marrow cells give rise to abnormally large osteoclasts even at concentrations of RANKL too low to induce osteoclast differentiation in wild-type cells and the number of nuclei per osteoclast is also increased relative to wild-type cells

increased osteoclast cell number ( J:117880 )

• increase in the numbers of osteoclasts in the jaws and femoral bone at 10 weeks of age

• increase in the fraction of the femoral trabecular bone perimeter that is occupied by osteoclasts

decreased bone mineral density ( J:117880 )

• decreased bone mineral density in the long bones at 10 weeks of age

decreased trabecular bone volume ( J:117880 )

• reduced trabecular bone volume, trabecular number, and to a lesser extent trabecular thickness are seen in long bones

abnormal compact bone morphology ( J:117880 )

• pitting of the cortical surface is seen particularly at the distal ends of limb bones

increased osteoblast cell number ( J:117880 )

• increase in the fraction of the femoral trabecular bone perimeter that is occupied by osteoblasts

decreased bone trabecula number ( J:117880 )

abnormal skeleton physiology ( J:117880 )

abnormal osteoclast physiology ( J:117880 )

• increase in resorptive activity on dentin slices compared to wild-type cells

joint inflammation ( J:117880 )

• in some mice infiltrates fill the synovial space of large joints and penetrate through the articular cartilage and underlying bone into the bone marrow

osteomyelitis ( J:117880 )

• cystic lesions are seen in the bones

• inflammatory lesions in the cortical regions of the long bones, maxilla, palate, and mandible

abnormal bone ossification ( J:117880 )

immune system

abnormal osteoclast differentiation ( J:117880 )

• bone marrow cells give rise to abnormally large osteoclasts even at concentrations of RANKL too low to induce osteoclast differentiation in wild-type cells and the number of nuclei per osteoclast is also increased relative to wild-type cells

abnormal B cell number ( J:117880 )

• increase in the proportion of B cells in the lymph nodes, bone marrow, and spleen

increased osteoclast cell number ( J:117880 )

• increase in the numbers of osteoclasts in the jaws and femoral bone at 10 weeks of age

• increase in the fraction of the femoral trabecular bone perimeter that is occupied by osteoclasts

abnormal macrophage physiology ( J:117880 )

• peritoneal macrophages from 10 week old mice display an increase in the proportion oc cells expressing TNF

abnormal osteoclast physiology ( J:117880 )

• increase in resorptive activity on dentin slices compared to wild-type cells

increased circulating tumor necrosis factor level ( J:117880 )

• serum levels of TNF are elevated to between 200 to 700 pg/ml while levels in wild-type and heterozygous mice are undetectable

abnormal immune system organ morphology ( J:117880 )

increased spleen red pulp amount ( J:117880 )

• increase in the size of the red pulp region

enlarged lymph nodes ( J:117880 )

• enlarged with increase in the size of medullary regions

increased inflammatory response ( J:117880 )

• swelling of the facial soft tissue resulting from inflammatory lesions

• infiltrates are macrophage rich and contain tartrate-resistant acidic phosphatase positive cells

stomach inflammation ( J:117880 )

• mice develop mild gastritis at 2 weeks of age

spinal cord inflammation ( J:117880 )

• spinal inflammation is observed at 7 weeks of age

blepharitis ( J:117880 )

• develop swollen eyelids resulting from inflammatory lesions starting around 6 weeks of age and this persists in mice until at least 30 weeks of age

joint inflammation ( J:117880 )

• in some mice infiltrates fill the synovial space of large joints and penetrate through the articular cartilage and underlying bone into the bone marrow

liver inflammation ( J:117880 )

• inflammation of the liver, consisting of small foci of neutrophils and macrophages, is seen at 1 week of age

• at 2 weeks of age mice develop more severe liver inflammation

myositis ( J:117880 )

• inflammation of the muscle and soft tissue associated with the craniofacial and long bones

osteomyelitis ( J:117880 )

• inflammatory lesions in the cortical regions of the long bones, maxilla, palate, and mandible

• cystic lesions are seen in the bones

lung inflammation ( J:117880 )

• inflammation of the lung, consisting of small foci of neutrophils and macrophages, is seen at 1 week of age

• at 2 weeks of age mice develop more severe lung inflammation

dermatitis ( J:117880 )

homeostasis/metabolism

increased circulating tumor necrosis factor level ( J:117880 )

• serum levels of TNF are elevated to between 200 to 700 pg/ml while levels in wild-type and heterozygous mice are undetectable

abnormal enzyme/coenzyme level ( J:117880 )

• elevated serum levels of tartrate-resistant acidic phosphatase

vision/eye

blepharitis ( J:117880 )

• develop swollen eyelids resulting from inflammatory lesions starting around 6 weeks of age and this persists in mice until at least 30 weeks of age

liver/biliary system

liver inflammation ( J:117880 )

• inflammation of the liver, consisting of small foci of neutrophils and macrophages, is seen at 1 week of age

• at 2 weeks of age mice develop more severe liver inflammation

muscle

myositis ( J:117880 )

• inflammation of the muscle and soft tissue associated with the craniofacial and long bones

digestive/alimentary system

stomach inflammation ( J:117880 )

• mice develop mild gastritis at 2 weeks of age

hematopoietic system

abnormal osteoclast differentiation ( J:117880 )

• bone marrow cells give rise to abnormally large osteoclasts even at concentrations of RANKL too low to induce osteoclast differentiation in wild-type cells and the number of nuclei per osteoclast is also increased relative to wild-type cells

abnormal B cell number ( J:117880 )

• increase in the proportion of B cells in the lymph nodes, bone marrow, and spleen

increased osteoclast cell number ( J:117880 )

• increase in the numbers of osteoclasts in the jaws and femoral bone at 10 weeks of age

• increase in the fraction of the femoral trabecular bone perimeter that is occupied by osteoclasts

increased spleen red pulp amount ( J:117880 )

• increase in the size of the red pulp region

abnormal macrophage physiology ( J:117880 )

• peritoneal macrophages from 10 week old mice display an increase in the proportion oc cells expressing TNF

abnormal osteoclast physiology ( J:117880 )

• increase in resorptive activity on dentin slices compared to wild-type cells

nervous system

spinal cord inflammation ( J:117880 )

• spinal inflammation is observed at 7 weeks of age

craniofacial

abnormal craniofacial bone morphology ( J:117880 )

abnormal neurocranium morphology ( J:117880 )

• reduced bone volume is seen at 10 weeks of age

abnormal jaw morphology ( J:117880 )

• reduced cortical bone thickness is seen at 10 weeks of age

• jaws display increased numbers of osteoclasts at 10 weeks of age

alveolar process atrophy ( J:117880 )

• loss of bone around teeth is seen at 10 weeks of age

respiratory system

lung inflammation ( J:117880 )

• inflammation of the lung, consisting of small foci of neutrophils and macrophages, is seen at 1 week of age

• at 2 weeks of age mice develop more severe lung inflammation

integument

dermatitis ( J:117880 )

cellular

abnormal osteoclast differentiation ( J:117880 )

• bone marrow cells give rise to abnormally large osteoclasts even at concentrations of RANKL too low to induce osteoclast differentiation in wild-type cells and the number of nuclei per osteoclast is also increased relative to wild-type cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cherubism		DOID:1856	OMIM:118400	J:117880

Genotype
MGI:3699095

ht2

• Allelic Composition: Sh3bp2^tm1Bjro/Sh3bp2⁺
• Genetic Background: involves: 129S4/SvJae * BALB/cJ * C57BL/6J

skeleton

abnormal osteoclast physiology ( J:117880 )

• increase in resorptive activity on dentin slices compared to wild-type cells

abnormal long bone morphology ( J:117880 )

• bone loss is detected in the long bones

abnormal bone structure ( J:117880 )

abnormal osteoclast differentiation ( J:117880 )

• bone marrow cells give rise to abnormally large osteoclasts even at concentrations of RANKL too low to induce osteoclast differentiation in wild-type cells and the number of nuclei per osteoclast is also increased relative to wild-type cells

increased osteoclast cell number ( J:117880 )

• increase in the numbers of osteoclasts in the jaws and femoral bone at 10 weeks of age

• increase in the fraction of the femoral trabecular bone perimeter that is occupied by osteoclasts

decreased trabecular bone volume ( J:117880 )

• reduced trabecular bone volume is seen in long bones; however trabecular thickness is similar to wild-type

abnormal compact bone morphology ( J:117880 )

• pitting of the cortical surface is seen particularly at the distal ends of limb bones

increased osteoblast cell number ( J:117880 )

• increase in the fraction of the femoral trabecular bone perimeter that is occupied by osteoblasts

decreased bone trabecula number ( J:117880 )

• reduced trabecular number is seen in long bones

abnormal bone ossification ( J:117880 )

immune system

immune system phenotype ( J:117880 )

N • unlike homozygous mice, heterozygotes do not develop enlarged lymph nodes, swelling of facial soft tissues, or elevated serum levels of TNF

abnormal osteoclast differentiation ( J:117880 )

• bone marrow cells give rise to abnormally large osteoclasts even at concentrations of RANKL too low to induce osteoclast differentiation in wild-type cells and the number of nuclei per osteoclast is also increased relative to wild-type cells

increased osteoclast cell number ( J:117880 )

• increase in the numbers of osteoclasts in the jaws and femoral bone at 10 weeks of age

• increase in the fraction of the femoral trabecular bone perimeter that is occupied by osteoclasts

abnormal osteoclast physiology ( J:117880 )

• increase in resorptive activity on dentin slices compared to wild-type cells

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:117880 )

• elevated serum levels of tartrate-resistant acidic phosphatase

hematopoietic system

abnormal osteoclast differentiation ( J:117880 )

• bone marrow cells give rise to abnormally large osteoclasts even at concentrations of RANKL too low to induce osteoclast differentiation in wild-type cells and the number of nuclei per osteoclast is also increased relative to wild-type cells

increased osteoclast cell number ( J:117880 )

• increase in the numbers of osteoclasts in the jaws and femoral bone at 10 weeks of age

• increase in the fraction of the femoral trabecular bone perimeter that is occupied by osteoclasts

abnormal osteoclast physiology ( J:117880 )

• increase in resorptive activity on dentin slices compared to wild-type cells

cellular

abnormal osteoclast differentiation ( J:117880 )

• bone marrow cells give rise to abnormally large osteoclasts even at concentrations of RANKL too low to induce osteoclast differentiation in wild-type cells and the number of nuclei per osteoclast is also increased relative to wild-type cells

Genotype
MGI:3831754

cn3

• Allelic Composition: Nfatc1^tm3Glm/Nfatc1^tm3Glm; Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

skeleton

skeleton phenotype ( J:144598 )

N • induction of cre at 10 days of age prevents the diffuse bone loss and focal cystic changes characteristic of mice homozygote for the Sh3bp2^tm1Bjro allele

abnormal osteoclast differentiation ( J:144598 )

• bone marrow cells fail to differentiate into osteoclasts in vitro

decreased osteoclast cell number ( J:144598 )

• a dramatic reduction in the number of TRAP⁺ cells is found iin the proximal humerus and distal femur

immune system

abnormal osteoclast differentiation ( J:144598 )

• bone marrow cells fail to differentiate into osteoclasts in vitro

stomach inflammation ( J:144598 )

• widespread inflammation is observed

decreased osteoclast cell number ( J:144598 )

• a dramatic reduction in the number of TRAP⁺ cells is found iin the proximal humerus and distal femur

lymph node inflammation ( J:144598 )

• widespread inflammation is observed

liver inflammation ( J:144598 )

• widespread inflammation is observed

lung inflammation ( J:144598 )

• widespread inflammation is observed

digestive/alimentary system

stomach inflammation ( J:144598 )

• widespread inflammation is observed

liver/biliary system

liver inflammation ( J:144598 )

• widespread inflammation is observed

respiratory system

lung inflammation ( J:144598 )

• widespread inflammation is observed

hematopoietic system

abnormal osteoclast differentiation ( J:144598 )

• bone marrow cells fail to differentiate into osteoclasts in vitro

decreased osteoclast cell number ( J:144598 )

• a dramatic reduction in the number of TRAP⁺ cells is found iin the proximal humerus and distal femur

cellular

abnormal osteoclast differentiation ( J:144598 )

• bone marrow cells fail to differentiate into osteoclasts in vitro

Genotype
MGI:3699096

cx4

• Allelic Composition: Rag1^tm1Mom/Rag1^tm1Mom; Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd * BALB/cJ * C57BL/6J

skeleton

abnormal osteoclast differentiation ( J:117880 )

• no change in abnormal osteoclast formation compared to mice homozygous for the Sh3bp2 allele alone

decreased bone mineral density ( J:117880 )

• decreased bone mineral density in the long bones at 10 weeks of age

• no improvement in bone loss compared to mice homozygous for the Sh3bp2 allele alone

immune system

abnormal osteoclast differentiation ( J:117880 )

• no change in abnormal osteoclast formation compared to mice homozygous for the Sh3bp2 allele alone

increased circulating tumor necrosis factor level ( J:117880 )

• serum levels of TNF are elevated similar to what is seen in mice homozygous for the Sh3bp2 allele alone

increased inflammatory response ( J:117880 )

• mice still develop the macrophage-rich inflammatory infiltrates in internal organs and periosteal regions that are seen in mice homozygous for the Sh3bp2 allele alone

homeostasis/metabolism

increased circulating tumor necrosis factor level ( J:117880 )

• serum levels of TNF are elevated similar to what is seen in mice homozygous for the Sh3bp2 allele alone

hematopoietic system

abnormal osteoclast differentiation ( J:117880 )

• no change in abnormal osteoclast formation compared to mice homozygous for the Sh3bp2 allele alone

cellular

abnormal osteoclast differentiation ( J:117880 )

• no change in abnormal osteoclast formation compared to mice homozygous for the Sh3bp2 allele alone

Genotype
MGI:3699098

cx5

• Allelic Composition: Csf1^op/Csf1^op; Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro
• Genetic Background: involves: 129S4/SvJae * BALB/cJ * C57BL/6J

skeleton

skeleton phenotype ( J:117880 )

N • the cortical bone resorption seen in mice homozygous for the Sh3bp2 allele alone is practically eliminated

immune system

increased circulating tumor necrosis factor level ( J:117880 )

• serum levels of TNF are elevated similar to what is seen in mice homozygous for the Sh3bp2 allele alone

abnormal lymph node cell ratio ( J:117880 )

• increase in macrophage numbers in the lymph nodes similar to what is seen in mice homozygous for the Sh3bp2 allele alone

liver inflammation ( J:117880 )

• inflammation is still present but the severity is greatly reduced compared to mice homozygous for the Sh3bp2 allele alone

• however, inflammation of the stomach mucosa seen in mice homozygous for the Sh3bp2 allele alone is practically eliminated

liver/biliary system

liver inflammation ( J:117880 )

• inflammation is still present but the severity is greatly reduced compared to mice homozygous for the Sh3bp2 allele alone

• however, inflammation of the stomach mucosa seen in mice homozygous for the Sh3bp2 allele alone is practically eliminated

homeostasis/metabolism

increased circulating tumor necrosis factor level ( J:117880 )

• serum levels of TNF are elevated similar to what is seen in mice homozygous for the Sh3bp2 allele alone

Genotype
MGI:3699099

cx6

• Allelic Composition: Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro; Tnf^tm1Gkl/Tnf^tm1Gkl
• Genetic Background: involves: 129S/SvEv * 129S4/SvJae * BALB/cJ * C57BL/6J

skeleton

skeleton phenotype ( J:117880 )

N • unlike in mice homozygous for the Sh3bp2 allele alone, trabecular and cortical bone loss are not seen

abnormal osteoclast differentiation ( J:117880 )

• bone marrow displays enhanced production of osteoclasts in response to cytokine stimulation, similar to mice homozygous for the Sh3bp2 allele alone

immune system

immune system phenotype ( J:117880 )

N • unlike in mice homozygous for the Sh3bp2 allele alone, lymph node abnormalities and systemic inflammation are not seen

abnormal osteoclast differentiation ( J:117880 )

• bone marrow displays enhanced production of osteoclasts in response to cytokine stimulation, similar to mice homozygous for the Sh3bp2 allele alone

hematopoietic system

abnormal osteoclast differentiation ( J:117880 )

• bone marrow displays enhanced production of osteoclasts in response to cytokine stimulation, similar to mice homozygous for the Sh3bp2 allele alone

cellular

abnormal osteoclast differentiation ( J:117880 )

• bone marrow displays enhanced production of osteoclasts in response to cytokine stimulation, similar to mice homozygous for the Sh3bp2 allele alone

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	cherubism	DOID:1856	OMIM:118400	J:117880