Phenotypes Associated with This Genotype

Genotype
MGI:4888122

• Allelic Composition: Klf15^tm1Jain/Klf15^tm1Jain
• Genetic Background: B6.129X1-Klf15^tm1Jain

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:121109 )

• unable to tolerate ascending aortic constriction (AAC) around a 27-gauge needle

• some mice die within 48 h postop of AAC using a 25-gauge needle

cardiovascular system

abnormal aorta morphology ( J:167880 )

• aortas from angiotensin II (AngII) infused mice display abnormalities consistent with induced aortopathy

abnormal aorta tunica adventitia morphology ( J:167880 )

• blunted adventitial growth response to AngII

abnormal aorta tunica media morphology ( J:167880 )

• abnormalities induced by AngII infusion include severe disruption of medial architecture characterized by prominent elastolysis, increased SMC apoptosis and reduced medial thickness

aortic hypertrophy ( J:167880 )

• mild medial hypertrophy

dilated aorta ( J:167880 )

• following AngII infusion

abdominal aorta aneurysm ( J:167880 )

• in some mice following AngII infusion

• development of abdominal aortic aneurysms is more common than development of thoracic aortic aneurysms

thoracic aorta aneurysm ( J:167880 )

• in some mice following AngII infusion

• development of abdominal aortic aneurysms is more common than development of thoracic aortic aneurysms

abnormal angiogenesis ( J:167880 )

• unlike in wild-type mice, AngII infusion fails to increase myocardial capillary density

increased myocardial fiber size ( J:121109 )

• following AAC with a 25-gauge needle myocytes are larger in area, longer and slightly narrower

enlarged heart ( J:167880 )

• infusion of AngII induces cardiomegaly

heart left ventricle hypertrophy ( J:167880 )

• mild

dilated heart ( J:121109 )

• increase in cavity size at 12-16 weeks of age

dilated heart left ventricle ( J:121109 )

• following AAC with a 25-gauge needle

increased susceptibility to induced aneurysm formation ( J:167880 )

• after AngII infusion, 35% of mice develop aortic aneurysm compared to 0% in wild-type mice

• development of abdominal aortic aneurysms is more common than development of thoracic aortic aneurysms

• some aneurysms develop intramural hematomas

decreased heart left ventricle muscle contractility ( J:121109 )

• decrease in left ventricular fractional shortening at 12-16 weeks of age

increased response of heart to induced stress ( J:121109 , J:167880 )

• unable to tolerate AAC around a 27-guage needle (J:121109)

• some mice die within 48 h postop of AAC using a 25-gauge needle (J:121109)

• AAC with a 25-gauge needle induces marked left ventricular dilation and reduction in systolic function (J:121109)

• hearts fail to increase left ventricular wall thickness following AAC with a 25-gauge needle (J:121109)

• increased sensitivity of the heart and aorta to AngII infusion (J:167880)

cardiomyopathy ( J:167880 )

• infusion of AngII induces severe cardiomyopathy characterized by cardiomegaly, LV dysfunction, and cavity dilation with attenuated wall thickening

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:129763 )

N • despite abnormalities in glucose homeostasis, no abnormalities in insulin levels are detected

increased response of heart to induced stress ( J:121109 , J:167880 )

• unable to tolerate AAC around a 27-guage needle (J:121109)

• some mice die within 48 h postop of AAC using a 25-gauge needle (J:121109)

• AAC with a 25-gauge needle induces marked left ventricular dilation and reduction in systolic function (J:121109)

• hearts fail to increase left ventricular wall thickness following AAC with a 25-gauge needle (J:121109)

• increased sensitivity of the heart and aorta to AngII infusion (J:167880)

abnormal circulating amino acid level ( J:129763 )

• increase in the concentrations of several amino acids including proline, tyrosine, leucine and valine

• decrease in the concentration of glutamine

decreased circulating glucose level ( J:129763 )

• small but significant decrease in blood glucose in ad libitum fed males and females compared to wild-type controls

hypoglycemia ( J:129763 )

• severe hypoglycemia after a 15h fast

increased circulating glucagon level ( J:129763 )

• in mice fasted for 18 h compared to similarly fasted wild-type mice

• however, no difference is detected in the fed state

increased circulating ketone body level ( J:129763 )

• elevated levels of beta-hydroxybutyrate in fasted mice

decreased circulating lactate level ( J:129763 )

• mild decrease in serum lactate levels in fed and fasted mice

abnormal gluconeogenesis ( J:129763 )

• during insulin clamp hepatic glucose production is reduced by 60% compared to controls

• significantly less efficient at utilizing alanine as a gluconeogenic substrate

improved glucose tolerance ( J:129763 )

• mice fasted for 16h clear glucose faster than wild-type controls

decreased liver glycogen level ( J:129763 )

• about 3.5 fold lower in mice fasted for 18 h compared to similarly fasted wild-type mice

• however, no difference is detected in the fed state

increased glycerol level ( J:129763 )

• in fed and fasted mice

ketoaciduria ( J:129763 )

• elevated acetoacetate levels in both fed and fasted mice

abnormal metabolism ( J:129763 )

• analysis suggests a decrease in amino acid breakdown

abnormal enzyme/coenzyme activity ( J:129763 )

• about a 2 fold reduction in alanine aminotransferase activity in hepatocytes

liver/biliary system

decreased liver glycogen level ( J:129763 )

• about 3.5 fold lower in mice fasted for 18 h compared to similarly fasted wild-type mice

• however, no difference is detected in the fed state

abnormal hepatocyte physiology ( J:129763 )

• decrease in alanine aminotransferase activity and glucose production

adipose tissue

decreased total body fat amount ( J:129763 )

• decreased fat mass at 4 months of age

growth/size/body

growth/size/body region phenotype ( J:129763 )

N • no significant differences in total body weight compared to wild-type mice are detected from 1 - 3.5 months of age

enlarged heart ( J:167880 )

• infusion of AngII induces cardiomegaly

heart left ventricle hypertrophy ( J:167880 )

• mild

increased lean body mass ( J:129763 )

• at 4 months of age

muscle

increased myocardial fiber size ( J:121109 )

• following AAC with a 25-gauge needle myocytes are larger in area, longer and slightly narrower

heart left ventricle hypertrophy ( J:167880 )

• mild

decreased heart left ventricle muscle contractility ( J:121109 )

• decrease in left ventricular fractional shortening at 12-16 weeks of age

cardiomyopathy ( J:167880 )

• infusion of AngII induces severe cardiomyopathy characterized by cardiomegaly, LV dysfunction, and cavity dilation with attenuated wall thickening

renal/urinary system

ketoaciduria ( J:129763 )

• elevated acetoacetate levels in both fed and fasted mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
aortic aneurysm		DOID:3627		J:167880