Mouse Genome Informatics
hm
    Mmp2tm1Ito/Mmp2tm1Ito
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
cardiovascular system
• mice exhibit 35% less ischemia-induced retinal neovascularization compared with similarly treated wild-type mice

skeleton
• hyperteloric with narrower, taller skulls
• overall skull lengths are decreased and about 10% shorter by 12 weeks of age
• area between the right and left frontal-squamosal intersection at the temporal crest, mid-cranial width, is wider and this difference increases with age
• mid-cranial width differences continue to increase from about 10% at 4 weeks to nearly 25% at 24 weeks
• coronal sutures are prominent and sclerotic
• lambdoid sutures are prominent and sclerotic
• sagittal sutures are prominent and sclerotic
• lower jaw length is about 10% shorter by 12 weeks of age
• upper jaw length is about 10% shorter by 12 weeks of age
• bone marrow has transiently decreased osteoclast numbers
• osteoblast and osteoclast numbers per trabecular bone surface area are decreased by more than half at 4 days of age, but no differences are seen at 4 and 12 weeks of age, indicating a transient decrease
• femoral condyles and proximal tibiae show cartilage destruction with erosions of cartilage occupied by fibrous tissue and inflammatory cells
• 6 month old mutants show a slight shortening of long bones
• progressive loss of bone mineral density; mutants begin to show loss at 5 weeks of age and show a 20% reduction at 10 weeks of age that persists throughout early adulthood, and with more rapid loss after 20 weeks of age
• 13.4% decrease in bone volume at 24 weeks of age
• defects in cortical bone formation in 4 day old mutants that appear to mostly resolve by 4 weeks of age
• cortical bone continues to show large areas of woven bone compared to normal lamellar tissue in wild-type bone at 4 and 12 weeks of age
• bone marrow has transiently decreased osteoblast numbers
• osteoblast and osteoclast numbers per trabecular bone surface area are decreased by more than half at 4 days of age, but no differences are seen at 4 and 12 weeks of age, indicating a transient decrease
• defects in trabecular bone formation in 4 day old mutants that appear to mostly resolve by 4 weeks of age
• primary spongiosa and trabeculae appear less dense and more scant
• knee joints of all 12 week old mutants show articular cartilage destruction and erosion of the underlying bone surface resulting in the loss of the smooth tibial and femoral surfaces
• bone of 4 day old mutants shows overall paucity and chaotic organization of trabecular bone, and marked hypocellularity and ragged metaphyseal and diaphyseal cortical bone, a phenotype seen in earlier embryological time points, indicating retarded bone growth
• stigmata of abnormal cortical growth remains at 4 weeks of age

craniofacial
• hyperteloric with narrower, taller skulls
• overall skull lengths are decreased and about 10% shorter by 12 weeks of age
• area between the right and left frontal-squamosal intersection at the temporal crest, mid-cranial width, is wider and this difference increases with age
• mid-cranial width differences continue to increase from about 10% at 4 weeks to nearly 25% at 24 weeks
• coronal sutures are prominent and sclerotic
• lambdoid sutures are prominent and sclerotic
• sagittal sutures are prominent and sclerotic
• lower jaw length is about 10% shorter by 12 weeks of age
• upper jaw length is about 10% shorter by 12 weeks of age
• broad snout
• snouts are about 15% shorter than wild-type at 4 weeks of age

growth/size
• broad snout
• snouts are about 15% shorter than wild-type at 4 weeks of age

hematopoietic system
• bone marrow has transiently decreased osteoclast numbers
• osteoblast and osteoclast numbers per trabecular bone surface area are decreased by more than half at 4 days of age, but no differences are seen at 4 and 12 weeks of age, indicating a transient decrease
• 60% decrease in the number of proliferating cells in the bone marrow at 4 days of age but not at 4 or 12 weeks of age
• bone marrow stromal cells and calvaria are unable to support osteoblast and osteoclast growth ex vivo

immune system
• bone marrow has transiently decreased osteoclast numbers
• osteoblast and osteoclast numbers per trabecular bone surface area are decreased by more than half at 4 days of age, but no differences are seen at 4 and 12 weeks of age, indicating a transient decrease
• femoral condyles and proximal tibiae show cartilage destruction with erosions of cartilage occupied by fibrous tissue and inflammatory cells

vision/eye
• mice exhibit 35% less ischemia-induced retinal neovascularization compared with similarly treated wild-type mice
• intercanthal distances are increased by about 10% at 4 weeks of age, however by 12 weeks of age, they are no longer statistically different

Mouse Models of Human Disease
OMIM IDRef(s)
Multicentric Osteolysis, Nodulosis, and Arthropathy; MONA 259600 J:121780