Phenotypes associated with this allele

• Allele Symbol: Ccm2^tm1Kwhi
• Allele Name: targeted mutation 1, Kevin Whitehead
• Allele ID: MGI:3817969
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ccm2^tm1Kwhi/Ccm2^tm1.1Kwhi Tg(Pdgfb-icre/ERT2,-EGFP)1Frut/?	involves: C57BL/6 * CBA	MGI:5052330
cn2	Ccm2^tm1Kwhi/Ccm2^tm1.1Kwhi Tg(Nes-cre)1Kln/0	involves: C57BL/6 * SJL	MGI:3838804
cn3	Ccm2^tm1Kwhi/Ccm2^tm1.1Kwhi Tg(Tek-cre)1Ywa/0	involves: C57BL/6 * SJL	MGI:3838812
cn4	Ccm2^tm1Kwhi/Ccm2^tm1Kwhi Tg(Nes-cre)1Kln/?	involves: C57BL/6 * SJL	MGI:5052329
cn5	Ccm2^tm1Kwhi/Ccm2^tm1.1Kwhi Tg(Tagln-cre)1Jjl/0	involves: FVB/N	MGI:3838805

Genotype
MGI:5052330

cn1

• Allelic Composition: Ccm2^tm1Kwhi/Ccm2^tm1.1Kwhi; Tg(Pdgfb-icre/ERT2,-EGFP)1Frut/?
• Genetic Background: involves: C57BL/6 * CBA

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

mortality/aging

postnatal lethality ( J:173947 )

• increased early mortality

cardiovascular system

abnormal brain vasculature morphology ( J:173947 )

• cerebral cavernous malformations develop as early as two months after tamoxifen treatment at 1 day of age

• most mice have lesions at 4 months and all mice at 6 months

• additional abnormalities include capillary telangiectasias, isolated caverns and multiple back to back caverns, thrombosis, hemorrhage, formation of secondary channels

• attenuation of endothelial cells in larger secondary channels but no gaps

abnormal pericyte morphology ( J:173947 )

• foot processes are missing

nervous system

abnormal brain vasculature morphology ( J:173947 )

• cerebral cavernous malformations develop as early as two months after tamoxifen treatment at 1 day of age

• most mice have lesions at 4 months and all mice at 6 months

• additional abnormalities include capillary telangiectasias, isolated caverns and multiple back to back caverns, thrombosis, hemorrhage, formation of secondary channels

• attenuation of endothelial cells in larger secondary channels but no gaps

CNS inflammation ( J:173947 )

• foci of mononuclear inflammatory cells also seen

abnormal astrocyte morphology ( J:173947 )

• foot processes are missing

immune system

CNS inflammation ( J:173947 )

• foci of mononuclear inflammatory cells also seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cerebral cavernous malformation 2		DOID:0060670	OMIM:603284	J:173947

Genotype
MGI:3838804

cn2

• Allelic Composition: Ccm2^tm1Kwhi/Ccm2^tm1.1Kwhi; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: C57BL/6 * SJL

normal phenotype

no abnormal phenotype detected ( J:146527 )

• no vasculature defects are observed during development

• homozygote mice are born at the expected ratios

Genotype
MGI:3838812

cn3

• Allelic Composition: Ccm2^tm1Kwhi/Ccm2^tm1.1Kwhi; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: C57BL/6 * SJL

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:146527 )

• mice die between E9-E10 from failed angiogenesis

embryo

abnormal pharyngeal arch morphology ( J:146527 )

abnormal first pharyngeal arch artery morphology ( J:146527 )

• the first branchial arch artery of E8.5 embryos fail to form a proper lumen

abnormal second pharyngeal arch artery morphology ( J:146527 )

• the second branchial arch artery of E8.5 embryos fail to form a proper lumen

abnormal third pharyngeal arch artery morphology ( J:146527 )

• the third branchial arch artery of E8.5 embryos fail to form a proper lumen

cardiovascular system

abnormal cardiovascular system morphology ( J:146527 )

dilated dorsal aorta ( J:146527 )

• the caudal portion of the dorsal aorta becomes enlarged in 8.5 embryos

abnormal first pharyngeal arch artery morphology ( J:146527 )

• the first branchial arch artery of E8.5 embryos fail to form a proper lumen

abnormal second pharyngeal arch artery morphology ( J:146527 )

• the second branchial arch artery of E8.5 embryos fail to form a proper lumen

abnormal third pharyngeal arch artery morphology ( J:146527 )

• the third branchial arch artery of E8.5 embryos fail to form a proper lumen

aorta stenosis ( J:146527 )

• adjacent portions of the aorta are also narrow and irregular

decreased angiogenesis ( J:146527 )

• the branchial arch arteries, the first essential angiogenic vessels, fail to form a stable lumen in E8.5 embryos

• the heart is not functionally connected with the vasculature, and circulation fails to initiate

poor circulation ( J:146527 )

• circulation is not established in E8.5 embryos

craniofacial

abnormal pharyngeal arch morphology ( J:146527 )

abnormal first pharyngeal arch artery morphology ( J:146527 )

• the first branchial arch artery of E8.5 embryos fail to form a proper lumen

abnormal second pharyngeal arch artery morphology ( J:146527 )

• the second branchial arch artery of E8.5 embryos fail to form a proper lumen

abnormal third pharyngeal arch artery morphology ( J:146527 )

• the third branchial arch artery of E8.5 embryos fail to form a proper lumen

Genotype
MGI:5052329

cn4

• Allelic Composition: Ccm2^tm1Kwhi/Ccm2^tm1Kwhi; Tg(Nes-cre)1Kln/?
• Genetic Background: involves: C57BL/6 * SJL

normal phenotype

no abnormal phenotype detected ( J:173947 )

• born alive with no obvious defects when the conditional deletion occurs in neural and glial tissue

Genotype
MGI:3838805

cn5

• Allelic Composition: Ccm2^tm1Kwhi/Ccm2^tm1.1Kwhi; Tg(Tagln-cre)1Jjl/0
• Genetic Background: involves: FVB/N

normal phenotype

no abnormal phenotype detected ( J:146527 )

• no vasculature defects are observed during development

• homozygote mice are born at the expected ratios