Phenotypes Associated with This Genotype

Genotype
MGI:2664355

• Allelic Composition: Col3a1^tm1Jae/Col3a1^tm1Jae
• Genetic Background: involves: 129S4/SvJae

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

Col3a1^tm1Jae/Col3a1^tm1Jae mouse with skin lesion

mortality/aging

premature death ( J:39273 )

• the average life span of surviving homozygotes was reduced to ~6 months or one-fifth of the normal life span, primarily due to ruptured blood vessels

postnatal lethality, incomplete penetrance ( J:39273 )

• most homozygotes died within the first 48 hr after birth

• the remaining homozygotes displayed an average survival rate of 5% at weaning age

cardiovascular system

cardiovascular system phenotype ( J:39273 )

N • homozygotes showed no obvious defects in the heart or midsize and small arteries

abnormal blood vessel morphology ( J:39273 )

• the sites of blood vessel rupture were sporadic and mostly associated with large vessels

abnormal aorta wall morphology ( J:39273 )

• the blood vessel rupture crossed the media leading to a blood-filled channel between media and adventitia and partially collapsed the lumen of the aorta

• the adventitia eventually ruptured elsewhere, and blood leaked into the peritoneal cavity

• the collagen fibrils located between smooth muscle cells or between smooth muscle cell and elastic fibers were absent or severely reduced in the media of aorta

• in a given area of the adventitia, the number of collagen fibrils was reduced to ~1/3 of wild-type, while the mean diameter of mutant fibrils was ~2-fold relative to wild-type

abnormal subendocardium layer morphology ( J:39273 )

• the collagen fibrils between epicardium and myocardium were reduced or missing

• the microvilli of the mutant epicardium appeared underdeveloped relative to wild-type

digestive/alimentary system

abnormal intestine morphology ( J:39273 )

• in addition to aneurysm, mutants showed frequent intestinal enlargement and occasional intestinal rupture resulting in death

• collagen fibrils were missing or highly reduced in the submucosa and serosa of mutant intestines

growth/size/body

decreased body size ( J:39273 )

• adult homozygous survivors appeared normal except that they were ~15% smaller than wild-type littermates of the same sex

liver/biliary system

abnormal liver morphology ( J:39273 )

• in mutant liver, the collagen I fibrils appeared disorganized and were highly variable in diameter

muscle

muscle phenotype ( J:39273 )

N • the overall arrangement of elastic fibers and smooth muscle cells appeared normal

respiratory system

abnormal lung morphology ( J:39273 )

• in mutant lung, the collagen I fibrils appeared disorganized and were highly variable in diameter

integument

abnormal cutaneous collagen fibril morphology ( J:39273 )

• as with the adventitia of the aorta, the collagen I fibrils in skin appeared disorganized and were highly variable in diameter

skin lesions ( J:39273 )

• about 60% of homozygotes displayed skin lesions

• the most severe lesions presented as open wounds of ~1 cm length in the shoulder area and penetrated the skin and exposed subdermal tissue

• the wounds were not due to fighting between animals

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
vascular type Ehlers-Danlos syndrome		DOID:14756	OMIM:130050	J:39273