Phenotypes Associated with This Genotype

Genotype
MGI:2387345

• Allelic Composition: Adipoq^tm1Ish/Adipoq^tm1Ish
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:106599 )

• mortality after transverse aortic constriction is significantly higher in homozygotes than wild-type due to acute or subacute heart failure

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:199264 )

N • mice exhibit normal insulin tolerance and ceramide content in bones

abnormal vascular wound healing ( J:79350 )

• severe neointimal thickening and proliferation of vascular smooth muscle cells in response to mechanical injury to femoral artery

abnormal energy homeostasis ( J:199264 )

increased susceptibility to diet-induced obesity ( J:103106 )

• on an atherogenic diet (high-fat/high-sucrose/high-salt) diet for 4 weeks, body weight is higher than in controls

increased energy expenditure ( J:199264 )

• in the dark and light cycle at 36 weeks

pulmonary edema ( J:106599 )

• seen in homozygotes that die after transverse aortic constriction

abnormal gas homeostasis ( J:199264 )

increased carbon dioxide production ( J:199264 )

• in the dark and light cycle at 36 weeks

increased oxygen consumption ( J:199264 )

• in the dark and light cycle at 36 weeks

abnormal glucose homeostasis ( J:199264 )

decreased insulin secretion ( J:199264 )

• glucose-stimulated at 12 weeks

increased circulating glucose level ( J:106599 )

• fasting glucose levels increase by 40% at 3 weeks after transverse aortic constriction compared to 20% in wild-type

hyperglycemia ( J:77479 , J:103106 )

• after two weeks on a high fat/high sucrose diet (J:77479)

• plasma glucose levels are higher than in wild-type after 4 weeks on a high-fat/high-sucrose/high-salt diet (J:103106)

impaired glucose tolerance ( J:199264 )

• at 12 weeks

insulin resistance ( J:77479 )

• after two weeks on a high fat/high sucrose diet

abnormal hormone level ( J:199264 )

increased circulating insulin level ( J:77479 )

• after two weeks on a high fat/high sucrose diet

increased circulating osteocalcin level ( J:199264 )

increased noradrenaline level ( J:199264 )

• increased noradrenaline level in the brain at 36 weeks

increased adiponectin level ( J:199264 )

• mice receiving adiponectin peripherally exhibit accumulation in the hypothalamus, brainstem, cortex, cerebellum and serum unlike in wild-type mice

increased circulating adiponectin level ( J:199264 )

• mice receiving adiponectin peripherally exhibit accumulation in the serum unlike in wild-type mice

abnormal lipid level ( J:77479 )

• disturbed free fatty acid clearance from plasma in basal state, taking longer than wild-type controls

increased circulating free fatty acids level ( J:77479 )

• after two weeks on a high fat/high sucrose diet

abnormal urine homeostasis ( J:199264 )

• increased in the urine at 6, 12 and 36 weeks

increased urine adrenaline level ( J:199264 )

• increased adrenaline level in the urine at 6, 12 and 36 weeks

skeleton

skeleton phenotype ( J:199264 )

N • mice exhibit normal bone resorption

abnormal skeleton morphology ( J:199264 )

abnormal osteoclast morphology ( J:199264 )

• increased osteoclast surface to bone surface at 36 weeks

decreased bone mineral density ( J:199264 )

• at 36 weeks

increased bone mineral density ( J:199264 )

• at 6 weeks

decreased trabecular bone volume ( J:199264 )

• at 36 weeks

increased trabecular bone volume ( J:199264 )

• at 6 and 12 weeks

increased compact bone thickness ( J:199264 )

• at 6 weeks

decreased osteoblast cell number ( J:199264 )

• at 36 weeks

increased osteoblast cell number ( J:199264 )

• 2-fold at 6 weeks

• however, this increase has largely vanished by 3 months

decreased bone trabecula number ( J:199264 )

• at 36 weeks

decreased bone mass ( J:199264 )

• at 9 months

increased bone mass ( J:199264 )

• affecting the axial and appendicular skeleton and the trabecular and cortical bones at 6 and, to a lesser extent, 12 weeks

abnormal skeleton physiology ( J:199264 )

abnormal osteoblast physiology ( J:199264 )

• mice exhibit increased proliferation of osteoblast progenitors in young mice, decreased osteoblast proliferation in older mice, decreased apoptosis in osteoblast and decreased oxidative stress in osteoblasts compared with wild-type mice

• however, treatment with adiponectin reduces proliferation and increases apoptosis

decreased bone ossification ( J:199264 )

• decreased bone formation rate at 36 weeks

increased bone ossification ( J:199264 )

• increased bone formation rate at 6 and 12 weeks

increased bone strength ( J:199264 )

• better biomechanical properties (increased peak load) than wild-type mice

cardiovascular system

abnormal cardiovascular system morphology ( J:106599 )

pulmonary vascular congestion ( J:106599 )

• 3 weeks after transverse aortic constriction, homozygotes exhibit greater pulmonary congestion than wild-type

vascular restenosis ( J:79350 )

• evident after mechanical injury to femoral artery

cardiac hypertrophy ( J:106599 )

• 3 weeks after transverse aortic constriction, homozygotes show a 110% increase in heart-to-body weight compared to 53% increase in wild-type and significantly larger cross-sectional surface area of cardiac myocytes indicating much more extensive hypertrophy than in wild-type

dilated heart left ventricle ( J:106599 )

• 3 weeks after transverse aortic constriction, homozygotes show greater left ventricle chamber dilation than wild-type

abnormal cardiovascular system physiology ( J:106599 )

hemorrhage ( J:106599 )

• seen in homozygotes that die after transverse aortic constriction

decreased ventricle muscle contractility ( J:106599 )

• 3 weeks after transverse aortic constriction, homozygotes show a larger decrease in left ventricular fractional shortening and left ventricular ejection fraction than wild-type

decreased heart rate ( J:199264 )

decreased systemic arterial blood pressure ( J:199264 )

increased systemic arterial systolic blood pressure ( J:103106 )

• increased compared to wild-type on a high-fat/high-sucrose/high-salt diet

abnormal vasodilation ( J:103106 )

• endothelium-dependent vasodilation in response to acetylcholine is significantly reduced compared to wild-type, however see no differences in endothelium-independent vasodilation in response to sodium nitroprusside

abnormal vascular wound healing ( J:79350 )

• severe neointimal thickening and proliferation of vascular smooth muscle cells in response to mechanical injury to femoral artery

congestive heart failure ( J:106599 )

• 3 weeks after transverse aortic constriction, homozygotes show exacerbated heart failure compared to wild-type controls

muscle

muscle phenotype ( J:199264 )

N • myoblasts exhibit normal proliferation and apoptosis

decreased ventricle muscle contractility ( J:106599 )

• 3 weeks after transverse aortic constriction, homozygotes show a larger decrease in left ventricular fractional shortening and left ventricular ejection fraction than wild-type

abnormal vasodilation ( J:103106 )

• endothelium-dependent vasodilation in response to acetylcholine is significantly reduced compared to wild-type, however see no differences in endothelium-independent vasodilation in response to sodium nitroprusside

respiratory system

pulmonary vascular congestion ( J:106599 )

• 3 weeks after transverse aortic constriction, homozygotes exhibit greater pulmonary congestion than wild-type

pulmonary edema ( J:106599 )

• seen in homozygotes that die after transverse aortic constriction

growth/size/body

cardiac hypertrophy ( J:106599 )

• 3 weeks after transverse aortic constriction, homozygotes show a 110% increase in heart-to-body weight compared to 53% increase in wild-type and significantly larger cross-sectional surface area of cardiac myocytes indicating much more extensive hypertrophy than in wild-type

decreased body weight ( J:199264 )

• at 9, but not 3, months

increased susceptibility to diet-induced obesity ( J:103106 )

• on an atherogenic diet (high-fat/high-sucrose/high-salt) diet for 4 weeks, body weight is higher than in controls

adipose tissue

abnormal abdominal fat pad morphology ( J:199264 )

• fat pad weight fails to increase over time as in wild-type mice

decreased total fat pad weight ( J:199264 )

• at 12 and 36 weeks

abnormal white adipose tissue morphology ( J:199264 )

• white adipose tissue exhibits increased expression of brown adipose tissue markers compared with wild-type tissue

behavior/neurological

decreased food intake ( J:199264 )

• slightly in older mice

cellular

abnormal osteoblast physiology ( J:199264 )

• mice exhibit increased proliferation of osteoblast progenitors in young mice, decreased osteoblast proliferation in older mice, decreased apoptosis in osteoblast and decreased oxidative stress in osteoblasts compared with wild-type mice

• however, treatment with adiponectin reduces proliferation and increases apoptosis

oxidative stress ( J:199264 )

• in osteoblasts

endocrine/exocrine glands

decreased insulin secretion ( J:199264 )

• glucose-stimulated at 12 weeks

hematopoietic system

abnormal osteoclast morphology ( J:199264 )

• increased osteoclast surface to bone surface at 36 weeks

immune system

abnormal osteoclast morphology ( J:199264 )

• increased osteoclast surface to bone surface at 36 weeks

liver/biliary system

liver/biliary system phenotype ( J:199264 )

N • hepatocytes exhibit normal proliferation and apoptosis

renal/urinary system

abnormal urine homeostasis ( J:199264 )

• increased in the urine at 6, 12 and 36 weeks

increased urine adrenaline level ( J:199264 )

• increased adrenaline level in the urine at 6, 12 and 36 weeks