Phenotypes Associated with This Genotype

Genotype
MGI:7536982

• Allelic Composition: Best3^tm1.1Zhoj/Best3^tm1.1Zhoj; Tg(Tagln-cre)1Her/0
• Genetic Background: involves: C57BL/6 * SJL

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:338981 )

• treatment with angiotensin II to induce hypertension induced mortality in 32.3% of mice, similar treatment induced no deaths in controls

premature death ( J:338981 )

• some die suddenly at 8 weeks of age

• gradual increase in mortality with age with 13 of 30 mice dying before 72 weeks of age

• treatment with ponatinib, which inhibits MEKK3 and MEKK2 signaling, increases survival rates

cardiovascular system

abnormal aorta morphology ( J:338981 )

abnormal aorta wall morphology ( J:338981 )

• false lumen formation, intramural hematomas and dissections at 8 weeks of age

• media thickness, disorganization, and decreased expression of cyto-skeletal protein are seen before and after angiotensin II treatment

abnormal aorta tunica media morphology ( J:338981 )

• decreased thickness

abnormal aorta elastic tissue morphology ( J:338981 )

• disruption and degradation of collagen and medial elastic lamina

decreased aorta wall thickness ( J:338981 )

• decreased medial thickness and degradation of the aortic wall

descending aorta dilation ( J:338981 )

• marked increase in diameter of the abdominal aorta at 8 weeks of age

dilated ascending aorta ( J:338981 )

• marked increase in diameter at 8 weeks of age

aortic dissection ( J:338981 )

• incidence increases with age

• develop aortic hematoma or dissection at 8 weeks of age

• at 24 weeks of age, aortic rupture across the intima and media, dissection of the aortic wall with blood collection between the media and fragmentation the elastic layers are seen

• about 63% of mice receiving angiotensin II develop serious dissections in the aorta arch and abdominal aorta, dissections do not develop in similarly treated controls

aortic aneurysm ( J:338981 )

• dilated aneurysms in the thoracic and abdominal aorta from 24 weeks of age

abdominal aorta aneurysm ( J:338981 )

• from 24 weeks of age

thoracic aorta aneurysm ( J:338981 )

• from 24 weeks of age

internal hemorrhage ( J:338981 )

• mice die of massive hemorrhage in the thoracic or peritoneal cavity

abnormal vascular smooth muscle physiology ( J:338981 )

• increased apoptosis of vascular smooth muscle cells in the aorta

aortitis ( J:338981 )

• increased numbers of CD68-positive macrophages in the aorta indicating involvement of inflammation in the development of aortic dissection

immune system

aortitis ( J:338981 )

• increased numbers of CD68-positive macrophages in the aorta indicating involvement of inflammation in the development of aortic dissection

cellular

increased apoptosis ( J:338981 )

• increased apoptosis of vascular smooth muscle cells in the aorta

muscle

abnormal vascular smooth muscle physiology ( J:338981 )

• increased apoptosis of vascular smooth muscle cells in the aorta

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
aortic dissection		DOID:0080685		J:338981