Phenotypes Associated with This Genotype

Genotype
MGI:4399118

• Allelic Composition: Timp3^tm1Osya/Timp3^tm1Osya
• Genetic Background: B6.129P2-Timp3^tm1Osya

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

renal/urinary system

abnormal kidney morphology ( J:154849 )

• following unilateral ureter obstruction, mice exhibit increased kidney size, distended renal tissue, unclear border between the outer and inner medulla, severe hydronephrosis, and smaller medulla to cortex ratio compared with similarly treated wild-type mice

enlarged kidney ( J:154849 )

• following unilateral ureter obstruction compared with similarly treated wild-type mice

hydronephrosis ( J:154849 )

• more severe following unilateral ureter obstruction compared to in similarly treated wild-type mice

homeostasis/metabolism

increased susceptibility to injury ( J:154849 )

• following unilateral ureter obstruction, mice exhibit increased kidney size, distended renal tissue, unclear border between the outer and inner medulla, severe hydronephrosis, and smaller medulla to cortex ratio compared with similarly treated wild-type mice

cardiovascular system

cardiovascular system phenotype ( J:154849 )

N • mice exhibit normal blood pressure and heart rate

abnormal aorta morphology ( J:193744 )

♂ • mutants exhibit adverse aortic remodeling after 2 weeks of angiotensin II infusion compared to wild-type mice, showing disorganized and disrupted elastin fibers and disorganized collagen structures, especially in the abdominal aorta

abnormal aorta wall morphology ( J:193744 )

♂ • angiotensin II infused mutants exhibit disrupted medial elastic lamellae and fibrillar structures in the abdominal aortic walls

abnormal abdominal aorta morphology ( J:193744 )

♂ • mutants treated with angiotensin II exhibit an increase in macrophage infiltration in the abdominal aorta and disrupted medial elastic lamellae and fibrillar structures in the abdominal aortic walls

abdominal aorta aneurysm ( J:193744 )

♂ • 60% of mutants develop abdominal aortic aneurysm after 4 weeks of angiotensin II infusion unlike wild-type mice, showing greater than 50% aortic dilation in the suprarenal region

♂ • treatment with a broad spectrum protease inhibitor, PD166793, during the course of angiotensin II infusion blocks abdominal aortic aneurysm development

abnormal blood vessel physiology ( J:193744 )

♂ • the aortic systolic expansion index, a measure of aortic elasticity and recoil property during systole and diastole is suppressed in the aneurysmal aorta of angiotensin II infused mutants

aortitis ( J:193744 )

♂ • mutants treated with angiotensin II exhibit an increase in macrophage infiltration in the abdominal aorta

immune system

aortitis ( J:193744 )

♂ • mutants treated with angiotensin II exhibit an increase in macrophage infiltration in the abdominal aorta

mortality/aging

premature death ( J:193744 )

♂ • survival is compromised after angiotensin II infusion due to aortic rupture, with mice showing 80-85% survival 28 days after infusion

growth/size/body

enlarged kidney ( J:154849 )

• following unilateral ureter obstruction compared with similarly treated wild-type mice