Phenotypes Associated with This Genotype

Genotype
MGI:3664639

• Allelic Composition: Fbln5^tm1Eno/Fbln5^tm1Eno
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

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

Vascular remodeling in Fbln5^tm1Eno/Fbln5^tm1Eno mice after 28 days of ligation

cardiovascular system

abnormal blood vessel elastic tissue morphology ( J:96831 )

• at 28 days after carotid artery ligation, mutant ligated vessels show an increased perimeter of both external and internal elastic lamina relative to wild-type ligated vessels; no differences are observed on non-ligated contralateral vessels

• ultrastructurally, neointima of ligated mutant vessels exhibit irregular and discontinuous elastic fibers, indicating disrupted assembly of neointimal elastic fibers

decreased angiogenesis ( J:159246 )

• tumors from pancreatic carcinoma cell line Pan02 injected subcutaneously exhibit reduced angiogenesis compared with tumors from cells injected into wild-type mice

abnormal blood vessel physiology ( J:96831 )

• at pressures >100 mmHg, homozygotes display reduced vessel extensibility of left carotid arteries relative to wild-type or heterozygous mice

abnormal vascular smooth muscle physiology ( J:96831 )

• at 28 days after carotid artery ligation, homozygotes exhibit SMC proliferation adjacent to the ligature

• in response to mitogenic stimulation by PDGF, primary SMCs isolated from aortas of P1 homozygotes show significantly enhanced proliferation and migration relative to wild-type cells; such responses are inhibited by overexpression of Fbln5

abnormal vascular wound healing ( J:96831 )

• in response to carotid artery ligation, homozygotes exhibit an exaggerated vascular remodeling response, as shown by increased vessel diameter and severe neointima formation with hypercellular thickened adventitia and thinning of the medial layer

homeostasis/metabolism

abnormal vascular wound healing ( J:96831 )

• in response to carotid artery ligation, homozygotes exhibit an exaggerated vascular remodeling response, as shown by increased vessel diameter and severe neointima formation with hypercellular thickened adventitia and thinning of the medial layer

increased susceptibility to induced thrombosis ( J:96831 )

• at 28 days after carotid artery ligation, homozygotes show a complex lesion of organized thrombus and SMC proliferation adjacent to the ligature

neoplasm

decreased metastatic potential ( J:159246 )

• tumors from pancreatic carcinoma cell line Pan02 injected subcutaneously exhibit reduced metastasis compared with tumors from cells injected into wild-type mice

decreased tumor growth/size ( J:159246 )

• tumors from pancreatic carcinoma cell line Pan02 injected subcutaneously exhibit reduced size, growth, proliferation, angiogenesis, and metastasis and increased apoptosis and reactive oxygen species compared with tumors from cells injected into wild-type mice

• however, tumor morphology is the same as in similarly treated wild-type mice

cellular

oxidative stress ( J:159246 )

• mouse embryonic fibroblasts exhibit increased integrin-induced reactive oxygen species production compared with similarly treated wild-type cells

muscle

abnormal vascular smooth muscle physiology ( J:96831 )

• at 28 days after carotid artery ligation, homozygotes exhibit SMC proliferation adjacent to the ligature

• in response to mitogenic stimulation by PDGF, primary SMCs isolated from aortas of P1 homozygotes show significantly enhanced proliferation and migration relative to wild-type cells; such responses are inhibited by overexpression of Fbln5