Mouse Genome Informatics
hm
    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