Mouse Genome Informatics
cn1
    Ccm2tm2.1Sbn/Ccm2tm2.1Sbn
Tg(Mx1-cre)1Cgn/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 3 of 6 mice treated with pIpC at 6 - 8 weeks of age died suddenly between 7 - 8 months of age

cardiovascular system
• cerebral cavernous malformation like vessels in pIpC treated mice were grossly dilated and exhibited an impaired and disrupted endothelial lumen structure
• cerebral cavernous malformation like lesions were detectable at 3 weeks after pIpC treatment
• all mice treated with pIpC at 6 - 8 weeks displayed prominent brain hemorrhages at over 7 months of age
• hemorrhages are widespread throughout the brain
• accumulation of hemosiderin in the brain neuronal damage were seen in association with lesions
• larger hemorrhages were visible most often in the cerebrum and cerebellum
• larger hemorrhages were visible most often in the cerebrum and cerebellum
• astrocyte abnormalities indicate an impaired blood-brain barrier in the region of cerebral cavernous malformation like lesions in pIpC treated mice

nervous system
• seizure like behavior was seen in 1 mouse, treated with pIpC at 6 - 8 weeks of age, at over 7 months of age
• cerebral cavernous malformation like vessels in pIpC treated mice were grossly dilated and exhibited an impaired and disrupted endothelial lumen structure
• cerebral cavernous malformation like lesions were detectable at 3 weeks after pIpC treatment
• all mice treated with pIpC at 6 - 8 weeks displayed prominent brain hemorrhages at over 7 months of age
• hemorrhages are widespread throughout the brain
• accumulation of hemosiderin in the brain neuronal damage were seen in association with lesions
• larger hemorrhages were visible most often in the cerebrum and cerebellum
• larger hemorrhages were visible most often in the cerebrum and cerebellum
• astrocyte abnormalities indicate an impaired blood-brain barrier in the region of cerebral cavernous malformation like lesions in pIpC treated mice
• microglia were recruited to cerebral cavernous malformation like lesions
• in pIpC treated mice astrocytes in the region of cerebral cavernous malformation like lesions astrocytes failed to extend their projections to surround capillaries and instead formed abnormal cell clusters

behavior/neurological
• in 1 mouse, treated with pIpC at 6 - 8 weeks of age, at over 7 months of age
• seizure like behavior was seen in 1 mouse, treated with pIpC at 6 - 8 weeks of age, at over 7 months of age

hematopoietic system
• microglia were recruited to cerebral cavernous malformation like lesions

immune system
• microglia were recruited to cerebral cavernous malformation like lesions

Mouse Models of Human Disease
OMIM IDRef(s)
Cerebral Cavernous Malformations 2; CCM2 603284 J:174085


Mouse Genome Informatics
cn2
    Ccm2tm2.1Sbn/Ccm2tm2.1Sbn
Tg(Tek-cre)1Ywa/0

involves: C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• expression analysis suggests that arteriogenesis is deficient
• at E9.5 no smooth muscle cells are detected around the dorsal aorta and no proper lumen is formed
• while the head and vitelline vascular plexi form they are not remodeled
• the dorsal aorta and posterior cardinal veins fuse with relatively little branching unlike in controls
• failure of remodeling
• at E9.5 no smooth muscle cells are detected around the dorsal aorta
• failure of endocardium expansion
• no or significantly deficient ventricular trabeculation
• incomplete looping

embryogenesis
• failure of remodeling
• less severe than in homozygous null mice

growth/size
• less severe than in homozygous null mice

muscle
• at E9.5 no smooth muscle cells are detected around the dorsal aorta

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Cerebral Cavernous Malformations 2; CCM2 603284 J:174085