Phenotypes associated with this allele

• Allele Symbol: Mus81^tm1Esse
• Allele Name: targeted mutation 1, Jeroen Essers
• Allele ID: MGI:3785405
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mus81^tm1Esse/Mus81^tm1Esse	involves: 129P2/OlaHsd * C57BL/6	MGI:3794044
hm2	Mus81^tm1Esse/Mus81^tm1Esse	involves: 129P2/OlaHsd * C57BL/6J	MGI:5661527
ht3	Mus81^tm1Esse/Mus81^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3794045
ht4	Mus81^tm1Esse/Mus81^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:5661526

Genotype
MGI:3794044

hm1

• Allelic Composition: Mus81^tm1Esse/Mus81^tm1Esse
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:133703 )

• several mice die suddenly before weaning from cardiovascular problems

• however, unlike homozygous null Efemp2 mice no prenatal lethality is seen

cardiovascular system

abnormal aorta morphology ( J:133703 )

• severely enlarged and tortuous aortas in all mice at 14 weeks of age

abnormal aorta wall morphology ( J:133703 )

• the ascending aorta show regions of relatively well organized laminae along with regions of dramatically affected laminae

abnormal aorta tunica adventitia morphology ( J:133703 )

• increased smooth muscle proliferation is seen especially in the tunica adventia of the aorta

abnormal aorta elastic tissue morphology ( J:133703 )

• the outer elastin layers have a granular appearance and the inner layers show fragmentation and disarray of the fibers

• disruption of elastic laminae is apparent at P1

increased aorta wall thickness ( J:133703 )

• accumulation of amorphous matrix material between elastic fibers results in aortic wall thickening

abnormal thoracic aorta morphology ( J:133703 )

• tortuous and elongated thoracic aorta

dilated ascending aorta ( J:133703 )

• dramatic dilation (2-fold increase in diameter) of the ascending aorta in all newborns

aortic dissection ( J:133703 )

• dissection of the thoracic aorta was seen in 2 mice that died suddenly

aortic aneurysm ( J:133703 )

heart left ventricle hypertrophy ( J:133703 )

• 50% increase in relative left ventricular mass

abnormal aortic valve morphology ( J:133703 )

aortic valve stenosis ( J:133703 )

• mild stenosis indicated by a small increase in the systolic pressure gradient across the aortic valve and in the transvalvular blood flow velocity

abnormal cardiovascular system physiology ( J:133703 )

abnormal blood flow velocity ( J:133703 )

• small increase in the transvalvular blood flow velocity

increased cardiac stroke volume ( J:133703 )

• increased stroke volume as a result of aortic insufficiency

internal hemorrhage ( J:133703 )

• signs of intramural bleeding are present in all mice at 14 weeks of age

hemopericardium ( J:133703 )

• hemopericardium causing cardiac tamponade was seen in 2 mice that died suddenly

aortic valve regurgitation ( J:133703 )

• determined by echo-Doppler measurements

abnormal heart ventricle pressure ( J:133703 )

• small increase in the systolic pressure gradient across the aortic valve

increased left ventricle diastolic pressure ( J:133703 )

• increased left ventricular end-diastolic pressure and diameter

increased pulse pressure ( J:133703 )

• 2- to 3-fold increase in aortic pulse pressure apparently the result of increased aortic stiffness

• however, no change is detected in heart rate or mean aortic pressure

homeostasis/metabolism

hemopericardium ( J:133703 )

• hemopericardium causing cardiac tamponade was seen in 2 mice that died suddenly

muscle

heart left ventricle hypertrophy ( J:133703 )

• 50% increase in relative left ventricular mass

growth/size/body

heart left ventricle hypertrophy ( J:133703 )

• 50% increase in relative left ventricular mass

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
arterial tortuosity syndrome		DOID:0050645	OMIM:208050	J:133703
Marfan syndrome		DOID:14323	OMIM:154700	J:133703

Genotype
MGI:5661527

hm2

• Allelic Composition: Mus81^tm1Esse/Mus81^tm1Esse
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

cardiovascular system

abnormal aorta morphology ( J:222498 )

• an increase in matrix metalloproteinases activation is seen in both the thoracic aorta and abdominal aorta

abnormal aorta tunica media morphology ( J:222498 )

• 3 month old mice show severe thickening and decellularization of the medial layer of the ascending aortic wall

abnormal aorta elastic tissue morphology ( J:222498 )

• 3 month old mice show fragmented and disorganized elastin laminae

ascending aorta aneurysm ( J:222498 )

• 2-3 fold dilated ascending aortic aneurysms in all mice

immune system

increased interleukin-1 beta secretion ( J:222498 )

• broncho-alveolar lavage shows higher levels of interleukin-1 beta

lung inflammation ( J:222498 )

• broncho-alveolar lavage indicates more inflammatory cells, particularly granulocytes (Gr-1+) and B-cells (CD19+) in the lungs

• cell suspensions of lungs contain more macrophages (F4/80+) and tend to contain more T-cells (CD3+) and dendritic cells (cD11c+)

• focal infiltrations of inflammatory cells are seen around veins and bronchi of adult lungs, consisting mainly of T-cells and dendritic cells

respiratory system

lung inflammation ( J:222498 )

• broncho-alveolar lavage indicates more inflammatory cells, particularly granulocytes (Gr-1+) and B-cells (CD19+) in the lungs

• cell suspensions of lungs contain more macrophages (F4/80+) and tend to contain more T-cells (CD3+) and dendritic cells (cD11c+)

• focal infiltrations of inflammatory cells are seen around veins and bronchi of adult lungs, consisting mainly of T-cells and dendritic cells

abnormal lung morphology ( J:222498 )

• graded increase in neutrophil elastase activity in the lungs

• newborn lungs show elastin abnormalities and adult lungs show interruptions in the elastin layers

• an increase in matrix metalloproteinases activation is seen in the lungs

overexpanded pulmonary alveolus ( J:222498 )

• alveolar airspace enlargement in both newborn and adult lungs

emphysema ( J:222498 )

• emphysematous changes are seen in lungs of newborns

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pulmonary emphysema		DOID:9675	OMIM:130700	J:222498

Genotype
MGI:3794045

ht3

• Allelic Composition: Mus81^tm1Esse/Mus81⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

cardiovascular system

abnormal aorta wall morphology ( J:133703 )

• subtle changes including reduction in translucence of the aortic wall

• accumulation of excess amorphous matrix material between elastic fibers; however, no defect in fiber integrity is seen

abnormal subclavian artery morphology ( J:133703 )

• abnormal ballooning of the proximal right subclavian artery

Genotype
MGI:5661526

ht4

• Allelic Composition: Mus81^tm1Esse/Mus81⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

cardiovascular system

abnormal aorta morphology ( J:222498 )

• an increase in matrix metalloproteinases activation is seen in both the thoracic aorta and abdominal aorta

abnormal aorta tunica media morphology ( J:222498 )

• aortas show increased medial thickness

abnormal aorta elastic tissue morphology ( J:222498 )

• aortas show signs of elastin breakage and increased deposition of amorphous cell material between the elastin layers

immune system

increased inflammatory response ( J:222498 )

• mice treated with LPS to mimic bacterial infection exhibit increased and prolonged inflammatory response compared to wild-type mice, showing a greater influx of macrophages, dendritic cells, T-cells, and granulocytes

respiratory system

abnormal lung morphology ( J:222498 )

• adult, but not neonatal, lungs show interruptions in the elastin layers

• graded increase in neutrophil elastase activity in the lungs

• an increase in matrix metalloproteinases activation is seen in the lungs

• however, inflammation in the lungs is not seen

overexpanded pulmonary alveolus ( J:222498 )

• alveolar airspace enlargement in adult lungs

emphysema ( J:222498 )

• mice acquire emphysematous changes with age