Mouse Genome Informatics
hm1
    Acvrl1tm2.1Spo/Acvrl1tm2.1Spo
involves: 129 * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mice are viable


Mouse Genome Informatics
cn2
    Acvrl1tm2.1Spo/Acvrl1tm2.1Spo
involves: 129
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• mice co-injected with a Cre recombinase and a VEGF expressing adenovirus exhibit malformed vessels and increased cerebrovascular density in the brain at the injection site resembling arteriovenous malformations
• co-injection of a Cre recombinase and a VEGF expressing adenovirus induces more cerebrovascular dysplasia in mutants than in similarly injected Engtm2.1Hma homozygotes, however gene deletion efficiency is higher in this mutant and when gene deletion efficiency is the same in both mutants, then this mutant shows fewer dysplastic vessels per gene copy than the Eng mutant
• however, mice co-injected with a Cre recombinase and a VEGF expressing adenovirus exhibit a similar degree of angiogenesis as in wild-type mice injected with the VEGF adenovirus

nervous system
• mice co-injected with a Cre recombinase and a VEGF expressing adenovirus exhibit malformed vessels and increased cerebrovascular density in the brain at the injection site resembling arteriovenous malformations
• co-injection of a Cre recombinase and a VEGF expressing adenovirus induces more cerebrovascular dysplasia in mutants than in similarly injected Engtm2.1Hma homozygotes, however gene deletion efficiency is higher in this mutant and when gene deletion efficiency is the same in both mutants, then this mutant shows fewer dysplastic vessels per gene copy than the Eng mutant
• however, mice co-injected with a Cre recombinase and a VEGF expressing adenovirus exhibit a similar degree of angiogenesis as in wild-type mice injected with the VEGF adenovirus

Mouse Models of Human Disease
OMIM IDRef(s)
Arteriovenous Malformations of the Brain 108010 J:196810


Mouse Genome Informatics
cn3
    Acvrl1tm2.1Spo/Acvrl1tm2.1Spo
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+

involves: 129 * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• adult mice administered with tamoxifen die 9-21 days after a single injection
• tamoxifen treated females show a shorter survival span than males

growth/size
• tamoxifen treated mutants show signs of illness such as slow movements, weight loss, pale paws, and low pO2 levels from 8-10 days after tamoxifen injection

cardiovascular system
• pulmonary arteries and veins are dilated
• high vascular permeability
• uterus shows signs of arteriovenous malformations in tamoxifen treated mutants
• mutants bearing excisional wounds on the dorsal skin and ear and treated with tamoxifen form arteriovenous shunts in the blood vessels near the wounds
• arteriovenous malformations in the GI tract of tamoxifen treated mutants are located in the Peyer's patches of small intestine and appendix
• in tamoxifen treated mutants
• in tamoxifen treated mutants
• tamoxifen treated mutants show signs of hemorrhages in the lungs

digestive/alimentary system
• arteriovenous malformations in the GI tract of tamoxifen treated mutants are located in the Peyer's patches of small intestine and appendix
• tamoxifen treated mutants exhibit darkened feces indicative of the presence of blood

hematopoietic system
• tamoxifen treated mutants exhibit reduced hematocrit
• in tamoxifen treated mutants

respiratory system
• pulmonary arteries and veins are dilated
• high vascular permeability
• tamoxifen treated mutants show signs of hemorrhages in the lungs

Mouse Models of Human Disease
OMIM IDRef(s)
Telangiectasia, Hereditary Hemorrhagic, Type 2; HHT2 600376 J:154620


Mouse Genome Informatics
cn4
    Acvrl1tm2.1Spo/Acvrl1tm2.1Spo
Tg(Acvrl1-cre)L1Spo/0

involves: 129 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• some die by P5

cardiovascular system
• blood vessels in the superficial layer of the GI tract appear to be dilated, disorganized and tortuous
• dilated, tortuous, irregular, and disorganized vessels in the small intestine
• mutant vessels show peculiar looping at the distal tip of blood vessels
• however, vascular abnormalities are not seen in the skin, heart, muscle, kidney, or large intestine
• blood vessels in the superficial layer of the brain appear to be dilated, disorganized and tortuous
• blood vessels in the superficial layer of the lung appear to be dilated, disorganized and tortuous
• abnormal looping vessels are seen in the lung
• dilated, irregular and disorganized vessels in the lungs with uneven and discontinuous smooth muscle layers
• highly permeable and leaky vessels in the lungs
• looping vessels consist of numerous arteriovenous fistulas
• presence of arteriovenous shunts as indicated by the presence of dye in both the venous and arterial branches
• arterioventricular shunting and diminished perfusion to distal microvessels is seen with dye injection
• lungs have numerous blood vessels with abnormal morphology and anterioventricular connections
• hemorrhages in the brain, lung, and GI tract
• dilated and hemorrhagic vessels in various brain areas, including the hippocampus
• dilated, convoluted, and tortuous vessels with signs of hemorrhage in the superficial layer of the lung

digestive/alimentary system

nervous system
• blood vessels in the superficial layer of the brain appear to be dilated, disorganized and tortuous

respiratory system
• blood vessels in the superficial layer of the lung appear to be dilated, disorganized and tortuous
• abnormal looping vessels are seen in the lung
• dilated, irregular and disorganized vessels in the lungs with uneven and discontinuous smooth muscle layers
• highly permeable and leaky vessels in the lungs
• dilated, convoluted, and tortuous vessels with signs of hemorrhage in the superficial layer of the lung

Mouse Models of Human Disease
OMIM IDRef(s)
Telangiectasia, Hereditary Hemorrhagic, Type 2; HHT2 600376 J:154620