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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Timp3tm1Osya
targeted mutation 1, Osamu Yasuda
MGI:4398972
Summary 4 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Timp3tm1Osya/Timp3tm1Osya B6.129P2-Timp3tm1Osya MGI:4399118
hm2
Timp3tm1Osya/Timp3tm1Osya involves: 129P2/OlaHsd * C57BL/6 MGI:4399117
hm3
Timp3tm1Osya/Timp3tm1Osya involves: 129P2/OlaHsd * C57BL/6J MGI:5617484
cx4
Mmp2tm1Ito/Mmp2tm1Ito
Timp3tm1Osya/Timp3tm1Osya
involves: 129P2/OlaHsd * C57BL/6 MGI:5516118


Genotype
MGI:4399118
hm1
Allelic
Composition
Timp3tm1Osya/Timp3tm1Osya
Genetic
Background
B6.129P2-Timp3tm1Osya
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Timp3tm1Osya mutation (0 available); any Timp3 mutation (18 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• 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
• following unilateral ureter obstruction compared with similarly treated wild-type mice
• more severe following unilateral ureter obstruction compared to in similarly treated wild-type mice

homeostasis/metabolism
• 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
N
• mice exhibit normal blood pressure and heart rate
• 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
• angiotensin II infused mutants exhibit disrupted medial elastic lamellae and fibrillar structures in the abdominal aortic walls
• 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
• 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
• 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
• mutants treated with angiotensin II exhibit an increase in macrophage infiltration in the abdominal aorta

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

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

growth/size/body
• following unilateral ureter obstruction compared with similarly treated wild-type mice




Genotype
MGI:4399117
hm2
Allelic
Composition
Timp3tm1Osya/Timp3tm1Osya
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Timp3tm1Osya mutation (0 available); any Timp3 mutation (18 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
N
• mice exhibit normal passive avoidance and active avoidance
• after several days in an open-field, mice fail to become accustomed to their environment, as determined by maintenance of novel environment locomotion and rearing levels, unlike similarly treated wild-type mice
• in a water maze test with invisible platform, mice exhibit reduced memory acquisition on day 2 compared with wild-type mice
• deficit in memory acquisition in a water maze test with invisible platform lessens with time
• however, by day 5 memory acquisition in a water maze with invisible platform is normal and performance in a water maze test with visible platform is normal

cardiovascular system
N
• whether or not infused with angiotensin II, mice exhibit normal heart rate
• disorganized extracellular matrix collagen fibers with reduced collagen I protein level in the carotid arteries of mice treated with angiotensin II
• however, doxycycline treatment prevents aberrant arterial extracellular matrix degradation
• disorganized and interrupted elastin fibers and lower elastin protein content in carotid arteries of mice treated with angiotensin II
• following angiotensin II infusion, mice fail to exhibit an increase in blood pressure as observed in wild-type mice
• following angiotensin II infusion, mesenteric arteries exhibit a reduced increase in media to lumen ratio with reduced medial thickness and increased lumen diameter compared with wild-type mice
• however, doxycycline treatment prevents reduction in media to lumen ratio
• following angiotensin II infusion, arteries are more distensible than in wild-type mice
• however, doxycycline treatment prevents reduction lumen dilation

muscle
• following angiotensin II infusion, arteries are more distensible than in wild-type mice
• however, doxycycline treatment prevents reduction lumen dilation




Genotype
MGI:5617484
hm3
Allelic
Composition
Timp3tm1Osya/Timp3tm1Osya
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Timp3tm1Osya mutation (0 available); any Timp3 mutation (18 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• mice exposed to a cold environment for 8 hours exhibit a higher core body temperature than wild-type mice, indicating enhanced adaptive thermogenesis
• mice exhibit higher body temperature
• however food intake, locomotor activity, respiratory exchange ratio and body weight are normal
• mice show higher carbon dioxide production at 15 weeks and 8 months of age
• mice show a greater increase in carbon dioxide production in response to treadmill-based exercise than wild-type mice
• mice show increased oxygen consumption at 15 weeks and 8 months of age
• mice show a greater increase in oxygen consumption in response to treadmill-based exercise than wild-type mice




Genotype
MGI:5516118
cx4
Allelic
Composition
Mmp2tm1Ito/Mmp2tm1Ito
Timp3tm1Osya/Timp3tm1Osya
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mmp2tm1Ito mutation (1 available); any Mmp2 mutation (25 available)
Timp3tm1Osya mutation (0 available); any Timp3 mutation (18 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
• angiotensin II infused mutants exhibit a greater disruption of the medial elastic lamellae and fibrillar structures in the abdominal aortic walls than in single Timp3 homozygotes
• angiotensin II infused mutants exhibit a greater disruption of the medial elastic lamellae and fibrillar structures in the abdominal aortic walls than in single Timp3 homozygotes
• 75% of mutants develop abdominal aortic aneurysm with greater than 50% aortic dilation in the suprarenal region after 4 weeks of angiotensin II infusion
• survival is compromised more than in single Timp3 homozygotes after angiotensin II infusion due to aortic rupture, with mice showing around 70% survival 28 days after infusion
• treatment with a broad spectrum protease inhibitor, PD166793, during the course of angiotensin II infusion blocks abdominal aortic aneurysm development
• mutants treated with angiotensin II exhibit heightened inflammation in the abdominal aorta, with enhanced infiltration of neutrophils and macrophages

immune system
• mutants treated with angiotensin II exhibit heightened inflammation in the abdominal aorta, with enhanced infiltration of neutrophils and macrophages

mortality/aging
• survival is compromised more than in single Timp3 homozygotes after angiotensin II infusion due to aortic rupture, with mice showing around 70% survival 28 days after infusion





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last database update
04/23/2024
MGI 6.23
The Jackson Laboratory