Phenotypes associated with this allele

• Allele Symbol: Ccm2^tm2.1Sbn
• Allele Name: targeted mutation 2.1, Ulrich Siebenlist
• Allele ID: MGI:5085315
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ccm2^tm2.1Sbn/Ccm2^tm2.1Sbn Tg(Mx1-cre)1Cgn/0	involves: C57BL/6 * CBA	MGI:5085321
cn2	Ccm2^tm2.1Sbn/Ccm2^tm2.1Sbn Tg(Tek-cre)1Ywa/0	involves: C57BL/6 * SJL	MGI:5085318

Genotype
MGI:5085321

cn1

• Allelic Composition: Ccm2^tm2.1Sbn/Ccm2^tm2.1Sbn; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: C57BL/6 * CBA

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

mortality/aging

premature death ( J:174085 )

• 3 of 6 mice treated with pIpC at 6 - 8 weeks of age died suddenly between 7 - 8 months of age

cardiovascular system

abnormal brain vasculature morphology ( J:174085 )

• 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

intracranial hemorrhage ( J:174085 )

• 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

cerebellum hemorrhage ( J:174085 )

• larger hemorrhages were visible most often in the cerebrum and cerebellum

intracerebral hemorrhage ( J:174085 )

• larger hemorrhages were visible most often in the cerebrum and cerebellum

impaired blood-brain barrier function ( J:174085 )

• astrocyte abnormalities indicate an impaired blood-brain barrier in the region of cerebral cavernous malformation like lesions in pIpC treated mice

nervous system

seizures ( J:174085 )

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

abnormal brain vasculature morphology ( J:174085 )

• 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

intracranial hemorrhage ( J:174085 )

• 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

cerebellum hemorrhage ( J:174085 )

• larger hemorrhages were visible most often in the cerebrum and cerebellum

intracerebral hemorrhage ( J:174085 )

• larger hemorrhages were visible most often in the cerebrum and cerebellum

impaired blood-brain barrier function ( J:174085 )

• astrocyte abnormalities indicate an impaired blood-brain barrier in the region of cerebral cavernous malformation like lesions in pIpC treated mice

microgliosis ( J:174085 )

• microglia were recruited to cerebral cavernous malformation like lesions

abnormal astrocyte morphology ( J:174085 )

• 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

ataxia ( J:174085 )

• in 1 mouse, treated with pIpC at 6 - 8 weeks of age, at over 7 months of age

seizures ( J:174085 )

• 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

microgliosis ( J:174085 )

• microglia were recruited to cerebral cavernous malformation like lesions

immune system

microgliosis ( J:174085 )

• microglia were recruited to cerebral cavernous malformation like lesions

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cerebral cavernous malformation 2		DOID:0060670	OMIM:603284	J:174085

Genotype
MGI:5085318

cn2

• Allelic Composition: Ccm2^tm2.1Sbn/Ccm2^tm2.1Sbn; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: C57BL/6 * SJL

cardiovascular system

abnormal artery development ( J:174085 )

• expression analysis suggests that arteriogenesis is deficient

abnormal dorsal aorta morphology ( J:174085 )

• at E9.5 no smooth muscle cells are detected around the dorsal aorta and no proper lumen is formed

abnormal developmental vascular remodeling ( J:174085 )

• while the head and vitelline vascular plexi form they are not remodeled

abnormal vascular branching morphogenesis ( J:174085 )

• the dorsal aorta and posterior cardinal veins fuse with relatively little branching unlike in controls

abnormal vascular smooth muscle morphology ( J:174085 )

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

abnormal heart development ( J:174085 )

• failure of endocardium expansion

• no or significantly deficient ventricular trabeculation

failure of heart looping ( J:174085 )

• incomplete looping

embryo

embryonic growth retardation ( J:174085 )

• less severe than in homozygous null mice

abnormal vitelline vascular remodeling ( J:174085 )

• failure of remodeling

growth/size/body

embryonic growth retardation ( J:174085 )

• less severe than in homozygous null mice

muscle

abnormal vascular smooth muscle morphology ( J:174085 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	cerebral cavernous malformation 2	DOID:0060670	OMIM:603284	J:174085