Phenotypes Associated with This Genotype

Genotype
MGI:3033418

• Allelic Composition: Acvrl1^tm1Enl/Acvrl1⁺
• Genetic Background: involves: C57BL/6

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

mortality/aging

premature death ( J:82115 )

• when allowed to live beyond 1 year of age, some heterozygotes die spontaneously, or are euthanized due to morbidity

cardiovascular system

cardiovascular system phenotype ( J:82115 )

N • at the age of >1 year, heterozygotes develop an age-dependent hereditary hemorrhagic telangiectasia (HHT)-like phenotype

dilated liver sinusoidal space ( J:82115 )

• sinusoidal capillaries are grossly dilated in affected liver lobes

hemorrhage ( J:82115 )

• the first and most frequently observed external manifestation of vascular pathology is the presence of discolored, cyanotic nailbeds and hemorrhage into claws

• histological examination of affected nailbeds revealed numerous closely packed telangiectases altering the adjacent bone

gastrointestinal hemorrhage ( J:82115 )

• some heterozygous mutants show visible gastrointestinal bleeding, as well as positive fecal occult blood tests

telangiectasia ( J:82115 )

• heterozygotes display vascular lesions (telangiectases) consisting of hyperdilated vessels with normal or thin walls, in isolation or in clusters, in normal or abnormal locations

• vascular lesions are observed in the skin, oral cavity, liver, spleen, lung, intestine and brain

• vascular lesions are often associated with hemorrhage, organ enlargement and/or fibrosis

• at least one vascular lesion is observed in ~40% of heterozygous mutant mice of a predominately C57BL/6 genetic background by the age of 12 months or older

digestive/alimentary system

gastrointestinal hemorrhage ( J:82115 )

• some heterozygous mutants show visible gastrointestinal bleeding, as well as positive fecal occult blood tests

liver/biliary system

abnormal hepatobiliary system morphology ( J:82115 )

• the range of gross liver lesions include focal lesions that are ~1-2 mm in diameter and consist of multiple thin-walled vessels that are hyperdilated and juxtaposed to each other

• liver lesions are the most predominant among vascular defects, and are associated with chronic hemorrhage, fibrosis, and morbidity

• one heterozygous mutant mouse with severe liver pathology, including hepatic arteriovenous malformations, also displayed a secondary cardiac phenotype, comprising of myocardial ischemia and loss

dilated liver sinusoidal space ( J:82115 )

• sinusoidal capillaries are grossly dilated in affected liver lobes

enlarged liver ( J:82115 )

muscle

telangiectasia ( J:82115 )

• heterozygotes display vascular lesions (telangiectases) consisting of hyperdilated vessels with normal or thin walls, in isolation or in clusters, in normal or abnormal locations

• vascular lesions are observed in the skin, oral cavity, liver, spleen, lung, intestine and brain

• vascular lesions are often associated with hemorrhage, organ enlargement and/or fibrosis

• at least one vascular lesion is observed in ~40% of heterozygous mutant mice of a predominately C57BL/6 genetic background by the age of 12 months or older

growth/size/body

enlarged liver ( J:82115 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary hemorrhagic telangiectasia		DOID:1270	OMIM:187300 OMIM:600376 OMIM:601101 OMIM:615506	J:82115