Phenotypes associated with this allele

• Allele Symbol: Fbln5^tm1Eno
• Allele Name: targeted mutation 1, Eric N Olson
• Allele ID: MGI:2681517
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fbln5^tm1Eno/Fbln5^tm1Eno	involves: 129S6/SvEvTac	MGI:2681526
hm2	Fbln5^tm1Eno/Fbln5^tm1Eno	involves: 129S6/SvEvTac * C57BL/6	MGI:3664639

Genotype
MGI:2681526

hm1

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

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

cardiovascular system

abnormal aorta morphology ( J:86754 )

• elongation and tortuosity of aorta

abnormal aorta elastic fiber morphology ( J:86754 )

• developmental defect associated with the organization of elastin fibers

abnormal aortic arch and aortic arch branch attachment ( J:86754 )

• elongated aorta results in the juxtaposition of brachiocephalic trunk and the left common carotid artery

abnormal ascending aorta morphology ( J:86754 )

• elongation of the ascending aorta, resulting in the juxtaposition of brachiocephalic trunk and the left common carotid artery

abnormal pulmonary circulation ( J:86754 )

abnormal systemic arterial blood pressure ( J:86754 )

• significant increase in systolic blood pressure at the aortic arch

• mean blood pressure and diastolic blood pressure did not differ from those of wild-type

respiratory system

abnormal pulmonary circulation ( J:86754 )

abnormal lung morphology ( J:86754 )

• lungs were observed to be expanded upon dissection

abnormal pulmonary alveolus morphology ( J:86754 )

• dilated alveoli, most severe in the peripheral regions of the lung

emphysema ( J:86754 )

• emphysematous change with the formation of peripheral bullae

abnormal terminal bronchiole morphology ( J:86754 )

• progressive enlargement of distal airspaces first evident at 2 weeks of age

integument

rough coat ( J:86754 )

• coinciding with increased looseness of skin around 50 days of age and becoming more pronounced with age

loose skin ( J:86754 )

• progressive looseness first noticeable by weaning

• excess folds of abdominal skin evident at 50 days of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cutis laxa		DOID:3144	OMIM:PS123700	J:86754

Genotype
MGI:3664639

hm2

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

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