Mouse Genome Informatics
hm1
    Sh3bp2tm1Bjro/Sh3bp2tm1Bjro
involves: 129S4/SvJae * BALB/cJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• impaired survival with age with only about 28% of homozygotes surviving to 30 weeks of age

skeleton
• reduced bone volume is seen at 10 weeks of age
• reduced cortical bone thickness is seen at 10 weeks of age
• jaws display increased numbers of osteoclasts at 10 weeks of age
• loss of bone around teeth is seen at 10 weeks of age
• bone loss is detected in the long bones
• 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
• 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 in the long bones at 10 weeks of age
• reduced trabecular bone volume, trabecular number, and to a lesser extent trabecular thickness are seen in long bones
• pitting of the cortical surface is seen particularly at the distal ends of limb bones
• increase in the fraction of the femoral trabecular bone perimeter that is occupied by osteoblasts
• increase in resorptive activity on dentin slices compared to wild-type cells
• in some mice infiltrates fill the synovial space of large joints and penetrate through the articular cartilage and underlying bone into the bone marrow
• inflammatory lesions in the cortical regions of the long bones, maxilla, palate, and mandible
• cystic lesions are seen in the bones

immune system
• 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
• increase in the proportion of B cells in the lymph nodes, bone marrow, and spleen
• 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
• peritoneal macrophages from 10 week old mice display an increase in the proportion oc cells expressing TNF
• increase in resorptive activity on dentin slices compared to wild-type cells
• serum levels of TNF are elevated to between 200 to 700 pg/ml while levels in wild-type and heterozygous mice are undetectable
• increase in the size of the red pulp region
• enlarged with increase in the size of medullary regions
• swelling of the facial soft tissue resulting from inflammatory lesions
• infiltrates are macrophage rich and contain tartrate-resistant acidic phosphatase positive cells
• mice develop mild gastritis at 2 weeks of age
• spinal inflammation is observed at 7 weeks of age
• 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
• in some mice infiltrates fill the synovial space of large joints and penetrate through the articular cartilage and underlying bone into the bone marrow
• 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
• inflammation of the muscle and soft tissue associated with the craniofacial and long bones
• inflammatory lesions in the cortical regions of the long bones, maxilla, palate, and mandible
• cystic lesions are seen in the bones
• 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

homeostasis/metabolism
• serum levels of TNF are elevated to between 200 to 700 pg/ml while levels in wild-type and heterozygous mice are undetectable
• elevated serum levels of tartrate-resistant acidic phosphatase

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

digestive/alimentary system
• mice develop mild gastritis at 2 weeks of age

hematopoietic system
• 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
• increase in the proportion of B cells in the lymph nodes, bone marrow, and spleen
• 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
• increase in the size of the red pulp region
• peritoneal macrophages from 10 week old mice display an increase in the proportion oc cells expressing TNF
• increase in resorptive activity on dentin slices compared to wild-type cells

nervous system
• spinal inflammation is observed at 7 weeks of age

craniofacial
• reduced bone volume is seen at 10 weeks of age
• reduced cortical bone thickness is seen at 10 weeks of age
• jaws display increased numbers of osteoclasts at 10 weeks of age
• loss of bone around teeth is seen at 10 weeks of age

respiratory system
• 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

cellular
• 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
OMIM IDRef(s)
Cherubism 118400 J:117880


Mouse Genome Informatics
ht2
    Sh3bp2tm1Bjro/Sh3bp2+
involves: 129S4/SvJae * BALB/cJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• increase in resorptive activity on dentin slices compared to wild-type cells
• bone loss is detected in the long bones
• 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
• 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
• reduced trabecular bone volume is seen in long bones; however trabecular thickness is similar to wild-type
• pitting of the cortical surface is seen particularly at the distal ends of limb bones
• increase in the fraction of the femoral trabecular bone perimeter that is occupied by osteoblasts
• reduced trabecular number is seen in long bones

immune system
N
• unlike homozygous mice, heterozygotes do not develop enlarged lymph nodes, swelling of facial soft tissues, or elevated serum levels of TNF (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
• 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
• increase in resorptive activity on dentin slices compared to wild-type cells

homeostasis/metabolism
• elevated serum levels of tartrate-resistant acidic phosphatase

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

cellular
• 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 Genome Informatics
cn3
    Nfatc1tm3Glm/Nfatc1tm3Glm
Sh3bp2tm1Bjro/Sh3bp2tm1Bjro
Tg(Mx1-cre)1Cgn/0

involves: 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
N
• induction of cre at 10 days of age prevents the diffuse bone loss and focal cystic changes characteristic of mice homozygote for the Sh3bp2tm1Bjro allele (J:144598)
• bone marrow cells fail to differentiate into osteoclasts in vitro
• a dramatic reduction in the number of TRAP+ cells is found iin the proximal humerus and distal femur

immune system
• bone marrow cells fail to differentiate into osteoclasts in vitro
• widespread inflammation is observed
• a dramatic reduction in the number of TRAP+ cells is found iin the proximal humerus and distal femur
• widespread inflammation is observed
• widespread inflammation is observed
• widespread inflammation is observed

digestive/alimentary system
• widespread inflammation is observed

liver/biliary system
• widespread inflammation is observed

respiratory system
• widespread inflammation is observed

hematopoietic system
• bone marrow cells fail to differentiate into osteoclasts in vitro
• a dramatic reduction in the number of TRAP+ cells is found iin the proximal humerus and distal femur

cellular
• bone marrow cells fail to differentiate into osteoclasts in vitro


Mouse Genome Informatics
cx4
    Sh3bp2tm1Bjro/Sh3bp2tm1Bjro
Tnftm1Gkl/Tnftm1Gkl

involves: 129S/SvEv * 129S4/SvJae * BALB/cJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
N
• unlike in mice homozygous for the Sh3bp2 allele alone, trabecular and cortical bone loss are not seen (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
N
• unlike in mice homozygous for the Sh3bp2 allele alone, lymph node abnormalities and systemic inflammation are not seen (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
• bone marrow displays enhanced production of osteoclasts in response to cytokine stimulation, similar to mice homozygous for the Sh3bp2 allele alone

cellular
• 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
OMIM IDRef(s)
NOT Cherubism 118400 J:117880


Mouse Genome Informatics
cx5
    Rag1tm1Mom/Rag1tm1Mom
Sh3bp2tm1Bjro/Sh3bp2tm1Bjro

involves: 129S4/SvJae * 129S7/SvEvBrd * BALB/cJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• no change in abnormal osteoclast formation compared to mice homozygous for the Sh3bp2 allele alone
• 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
• no change in abnormal osteoclast formation compared to mice homozygous for the Sh3bp2 allele alone
• serum levels of TNF are elevated similar to what is seen in mice homozygous for the Sh3bp2 allele alone
• 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
• serum levels of TNF are elevated similar to what is seen in mice homozygous for the Sh3bp2 allele alone

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

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


Mouse Genome Informatics
cx6
    Csf1op/Csf1op
Sh3bp2tm1Bjro/Sh3bp2tm1Bjro

involves: 129S4/SvJae * BALB/cJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
N
• the cortical bone resorption seen in mice homozygous for the Sh3bp2 allele alone is practically eliminated (J:117880)

immune system
• serum levels of TNF are elevated similar to what is seen in mice homozygous for the Sh3bp2 allele alone
• increase in macrophage numbers in the lymph nodes similar to what is seen in mice homozygous for the Sh3bp2 allele alone
• 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
• 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
• serum levels of TNF are elevated similar to what is seen in mice homozygous for the Sh3bp2 allele alone