Phenotypes associated with this allele

• Allele Symbol: Eln^tm1Dyl
• Allele Name: targeted mutation 1, Dean Y Li
• Allele ID: MGI:2153007
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Eln^tm1Dyl/Eln^tm1Dyl	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3619991
ht2	Eln^tm1Dyl/Eln^+	B6.129-Eln^tm1Dyl	MGI:3620001
ht3	Eln^tm1Dyl/Eln^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5428443
ht4	Eln^tm1Dyl/Eln^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3619994
ht5	Eln^tm1Dyl/Eln^+	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3664640
cx6	Eln^tm1Dyl/Eln^+ Mgp^tm1Kry/Mgp^tm1Kry	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ	MGI:5556199

Genotype
MGI:3619991

hm1

• Allelic Composition: Eln^tm1Dyl/Eln^tm1Dyl
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

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

mortality/aging

postnatal lethality, complete penetrance ( J:47771 , J:110736 )

• die by P4.5 of an obstructive arterial disease (J:47771)

• no homozygotes survive past P3.5 (J:110736)

cardiovascular system

abnormal artery morphology ( J:47771 )

• increase in cellularity and reduction in luminal diameter in systemic and pulmonary arteries of all sizes, including distributing arteries and arterioles

abnormal artery development ( J:47771 )

• abnormal development of several different arteries (pulmonary arteriole, internal mammary artery, subclavian artery, and abdominal aorta)

abnormal pulmonary artery morphology ( J:47771 )

• increase in cellularity and reduction in luminal diameter

abnormal aorta wall morphology ( J:47771 )

• inner and outer diameters of the aorta become progressively smaller, starting at E17.5

• by P2.5, show a 76% increase in the number of cells in the aorta resulting in subendothelial accumulation of cells that eventually obliterates the vascular lumen

increased aorta wall thickness ( J:47771 )

• the arterial wall becomes progressively thicker, starting at E17.5

abnormal subclavian artery morphology ( J:47771 )

• increase in cellularity and reduction in luminal diameter

artery stenosis ( J:47771 )

• arterial diameter decreases due to subendothelial accumulation of arterial smooth muscle, eventually leading to obliteration of the lumen

abnormal vascular smooth muscle morphology ( J:47771 )

• accumulation of smooth muscle in arteries due to increased subendothelial proliferation

• reorientation of smooth muscle in arteries

muscle

abnormal vascular smooth muscle morphology ( J:47771 )

• accumulation of smooth muscle in arteries due to increased subendothelial proliferation

• reorientation of smooth muscle in arteries

respiratory system

abnormal lung development ( J:110736 )

• perinatal development of terminal airway branches is arrested

impaired lung alveolus development ( J:110736 )

• exhibit no increase in the number of distal air sacs between E18.5 and P0.5 as in wild-type

• radial alveolar count (RAC) fails to increase between E18.5 and P0.5 as in wild-type

• exhibit a decrease in secondary crest volume density during alveolization instead of the increase that is seen in wild-type

atelectasis ( J:110736 )

• by P2.5, areas of atelectasis are occasionally dispersed among the bullous-like lung tissue

overexpanded pulmonary alveolus ( J:110736 )

• at birth, lungs have larger distal air sacs and thinner surrounding walls

• at P0.5, the distal air sacs continue to expand, causing the intervening wall tissue to become progressively thinner

emphysema ( J:110736 )

• fewer distal air sacs that are dilated with attenuated tissue septae, a condition reminiscent of emphysema

Genotype
MGI:3620001

ht2

• Allelic Composition: Eln^tm1Dyl/Eln⁺
• Genetic Background: B6.129-Eln^tm1Dyl

cardiovascular system

abnormal artery morphology ( J:86535 )

• increase in arterial stiffness

decreased aorta elastin content ( J:86535 )

• elastin levels are about 35% lower in the ascending and abdominal aorta

decreased aorta wall thickness ( J:86535 )

• 20-25% decrease in wall thickness of the aorta at physiological mean arterial pressure

artery stenosis ( J:86535 )

• inner and outer diameters of arteries are smaller at any given intravascular pressure

cardiac hypertrophy ( J:86535 )

• develop only moderate cardiac hypertrophy (15% increase in heart weight), however, do not show signs of degenerative vascular disease

abnormal cardiovascular system physiology ( J:86535 )

increased cardiac output ( J:86535 )

increased cardiac stroke volume ( J:86535 )

• increase in cardiac output volume

hypertension ( J:86535 )

• hypertensive from birth

increased mean systemic arterial blood pressure ( J:86535 )

• mean arterial pressure is 25-30 mmHg higher than in wild-type

increased systemic arterial diastolic blood pressure ( J:86535 )

increased systemic arterial systolic blood pressure ( J:86535 )

abnormal blood vessel physiology ( J:86535 )

• at their higher physiological pressure, vessels are stiffer and have a higher circumferential wall stress, circumferential wall strain, and incremental elasticity modulus than wild-type vessels

• at lower pressures, however, vessels are more elastic and show greater dilation than wild-type arteries

• undergo normal vasoconstriction in response to phenylephrine and normal vasodilation in response to acetylcholine

homeostasis/metabolism

increased circulating renin level ( J:86535 )

• more than 2-fold increase in plasma renin levels, however aldosterone levels were similar to wild-type

growth/size/body

cardiac hypertrophy ( J:86535 )

• develop only moderate cardiac hypertrophy (15% increase in heart weight), however, do not show signs of degenerative vascular disease

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
essential hypertension		DOID:10825	OMIM:145500 OMIM:603918 OMIM:604329 OMIM:607329 OMIM:608742 OMIM:610261 OMIM:610262 OMIM:610948 OMIM:611014	J:86535
supravalvular aortic stenosis		DOID:1929	OMIM:185500	J:86535

Genotype
MGI:5428443

ht3

• Allelic Composition: Eln^tm1Dyl/Eln⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

cardiovascular system

abnormal aortic valve morphology ( J:184494 )

• aged mutants exhibit extracellular matrix abnormalities such as an increase in cleaved versican in the cusp and annulus regions, increase in total proteoglycan content and decrease in type I and III collagens in the aortic valves

abnormal aortic valve annulus morphology ( J:184494 )

• aortic valves exhibit extracellular matrix structural abnormalities including proteoglycan accumulation in the annulus region and abnormal cartilage-like nodule formation in subareas of the annulus, specifically near the commissures and aortic-mitral continuity

• nodules are characterized by chondrocyte-like halo-cell morphology and are seen at all stages, indicating a developmental abnormality preceding the development of aortic valve disease

• proteoglycan accumulation is seen only in aged mutants

• MMP expression in the annulus indicates early maladaptive extracellular matrix (ECM) remodeling in aortic valve malformation without aortic valve disease and worsening pathologic ECM remodeling with aortic valve disease

abnormal cardiovascular system physiology ( J:184494 )

• aortic valves show a progressive decrease in regional tissue tensile stiffness

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
aortic valve disease		DOID:62		J:184494

Genotype
MGI:3619994

ht4

• Allelic Composition: Eln^tm1Dyl/Eln⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

Thinner and abnormal elastic lamellae in the ascending aorta of Eln^tm1Dyl/Eln⁺ mice

cardiovascular system

abnormal blood vessel elastic tissue morphology ( J:51109 )

• elastic lamellae are thinner and increased in number in arteries

abnormal aorta elastic tissue morphology ( J:51109 )

• elastic lamellae in the aorta are about 50% thinner

• 5% and 25% increase in elastic lamellae in the descending and ascending aorta, respectively

decreased aorta elastin content ( J:51109 )

• 50% decrease

abnormal vascular smooth muscle morphology ( J:51109 )

• 35% increase in smooth muscle and elastic lamellae in arteries

abnormal blood vessel physiology ( J:51109 )

• although at physiologic pressures, aortae have normal extensibility, at 125 mmHg and above, aortic extensibility is reduced

muscle

abnormal vascular smooth muscle morphology ( J:51109 )

• 35% increase in smooth muscle and elastic lamellae in arteries

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
supravalvular aortic stenosis		DOID:1929	OMIM:185500	J:51109

Genotype
MGI:3664640

ht5

• Allelic Composition: Eln^tm1Dyl/Eln⁺
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6

Reduced vessel extensibility in the Fbln5^tm1Eno/Fbln5^tm1Eno and Eln^tm1Dyl/Eln⁺ carotid artery

cardiovascular system

abnormal blood vessel elastic tissue morphology ( J:96831 )

• at 28 days after carotid artery ligation, heterozygous ligated vessels show a slight reduction in the thickness of the medial wall with no changes in intima/media ratio or in the perimeter of external/internal elastic lamina relative to wild-type ligated vessels

• in contrast, nonligated contralateral heterozygous vessels show an increase in wall thickness and a decrease in internal and external elastic lamina perimeter relative to wild-type vessels

abnormal blood vessel physiology ( J:96831 )

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

abnormal vascular wound healing ( J:96831 )

• unexpectedly, heterozygotes do not exhibit exacerbated outward remodeling after 28 days of carotid artery ligation, and the degree of neointima formation is significantly less than that observed in homozygous Fbln5^tm1Eno mice despite a similar reduction in vessel extensibility at >100 mmHg

homeostasis/metabolism

abnormal vascular wound healing ( J:96831 )

• unexpectedly, heterozygotes do not exhibit exacerbated outward remodeling after 28 days of carotid artery ligation, and the degree of neointima formation is significantly less than that observed in homozygous Fbln5^tm1Eno mice despite a similar reduction in vessel extensibility at >100 mmHg

Genotype
MGI:5556199

cx6

• Allelic Composition: Eln^tm1Dyl/Eln⁺; Mgp^tm1Kry/Mgp^tm1Kry
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ

cardiovascular system

calcified artery ( J:203924 )

• progression of arterial calcification is delayed compared to single Mgp homozygotes

skeleton

abnormal epiphyseal plate morphology ( J:203924 )

• vertebral growth plates are abnormally calcified

• however, bone volume, trabecular and cortical bone mass, osteoblast and osteoclast counts, and bone formation are normal at 5 weeks of age