Phenotypes associated with this allele

• Allele Symbol: Cd36^tm1Mfe
• Allele Name: targeted mutation 1, Maria Febbraio
• Allele ID: MGI:1931790
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cd36^tm1Mfe/Cd36^tm1Mfe	B6.129S1-Cd36^tm1Mfe	MGI:4888252
hm2	Cd36^tm1Mfe/Cd36^tm1Mfe	involves: 129S1/Sv	MGI:4888253
hm3	Cd36^tm1Mfe/Cd36^tm1Mfe	involves: 129S1/Sv * C57BL/6	MGI:3587412
cx4	Apoe^tm1Unc/Apoe^tm1Unc Cd36^tm1Mfe/Cd36^tm1Mfe	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6	MGI:4888254

Genotype
MGI:4888252

hm1

• Allelic Composition: Cd36^tm1Mfe/Cd36^tm1Mfe
• Genetic Background: B6.129S1-Cd36^tm1Mfe

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

growth/size/body

decreased body weight ( J:87372 )

• significantly lower body weight

cardiovascular system

abnormal choriocapillaris morphology ( J:281382 )

• choriocapillaries of 12-month old homozygous mice show capillary dropout and a moth-eaten appearance

• increase in avascular area of choroids of 12-month old mice; first apparent at 4 months of age

• severe thinning or absence of choroids at 12 months of age

nervous system

abnormal retina photoreceptor morphology ( J:281382 )

• ill-defined limit between inner and outer photoreceptor segments

disorganized photoreceptor outer segment ( J:281382 )

• outer segments are irregular and accumulate in some areas as seen in periodic acid Schiff stains

• outer segments are detached from the retinal pigment epithelium villi

vision/eye

abnormal choriocapillaris morphology ( J:281382 )

• choriocapillaries of 12-month old homozygous mice show capillary dropout and a moth-eaten appearance

• increase in avascular area of choroids of 12-month old mice; first apparent at 4 months of age

• severe thinning or absence of choroids at 12 months of age

abnormal retina photoreceptor morphology ( J:281382 )

• ill-defined limit between inner and outer photoreceptor segments

disorganized photoreceptor outer segment ( J:281382 )

• outer segments are irregular and accumulate in some areas as seen in periodic acid Schiff stains

• outer segments are detached from the retinal pigment epithelium villi

thin retina outer nuclear layer ( J:281382 )

• semi-thin retinal sections of 12-month old homozygous mice show a thin irregular outer nuclear layer

disorganized retina outer nuclear layer ( J:281382 )

behavior/neurological

abnormal food intake ( J:87372 )

• lower food intake

abnormal food preference ( J:102503 )

• loss of normal preference for linoleic acid solutions

• reduced preference for solid diets enriched with long-chain fatty acids

homeostasis/metabolism

increased circulating ketone body level ( J:87372 )

• plasma ketone bodies are increased

decreased susceptibility to induced thrombosis ( J:136325 )

• time to complete thrombotic occlusion resulting from 7.5% FeCl3 treatment of the carotid artery is doubled relative to controls

• using a 12.5% dose of FeCl3, thrombotic occlusion time is essentially identical to controls

• reduced endothelial microparticle incorporation into thrombi

abnormal glucose homeostasis ( J:87372 )

• tend to have a higher whole body glucose uptake, but not significant

• glucose uptake significantly increased during a hyperinsulinemia clamp

• glucose uptake increases in skeletal muscle but not in adipose tissue

• increased basal glucose oxidation

• muscle glycogen is normal

abnormal gluconeogenesis ( J:87372 )

• endogenous glucose production increases more during hyperinsulinemia

• insulin does not inhibit glucose production in the liver

abnormal lipid level ( J:87372 )

abnormal circulating lipid level ( J:87372 )

increased circulating triglyceride level ( J:87372 )

abnormal fatty acids level ( J:87372 )

decreased fatty acids level ( J:87372 )

• decreased fatty acid uptake in muscle after an overnight fast

decreased liver free fatty acids level ( J:135594 )

• after three day gavage with LXR agonists

increased fatty acids level ( J:87372 )

• increased fatty acid uptake in the liver after an overnight fast

increased circulating free fatty acids level ( J:87372 )

decreased liver triglyceride level ( J:135594 )

• after three day gavage with LXR agonists

increased liver triglyceride level ( J:87372 )

• after an overnight fast

endocrine/exocrine glands

abnormal exocrine pancreas physiology ( J:102503 )

• pancreatobiliary flux and protein content are not induced by linoleic acid intake as occurs in controls

immune system

abnormal B cell morphology ( J:130897 )

increased transitional stage B cell number ( J:130897 )

• slight increase in spleen and bone marrow transitional B cells

abnormal plasma cell differentiation ( J:130897 )

• reduced plasma cell generation

decreased immunoglobulin level ( J:130897 )

decreased IgG level ( J:130897 )

• non-statistical reductions in IgG response to particulate antigens

decreased IgG1 level ( J:130897 )

decreased IgG2a level ( J:130897 )

decreased IgG2c level ( J:130897 )

decreased IgM level ( J:130897 )

• response to particulate antigens is reduced to 65% of normal at 7 days

liver/biliary system

decreased liver free fatty acids level ( J:135594 )

• after three day gavage with LXR agonists

decreased liver triglyceride level ( J:135594 )

• after three day gavage with LXR agonists

increased liver triglyceride level ( J:87372 )

• after an overnight fast

abnormal liver physiology ( J:135594 )

• dramatically reduced LXR agonists induce hepatic lipid accumulation

digestive/alimentary system

abnormal exocrine pancreas physiology ( J:102503 )

• pancreatobiliary flux and protein content are not induced by linoleic acid intake as occurs in controls

hematopoietic system

abnormal B cell morphology ( J:130897 )

increased transitional stage B cell number ( J:130897 )

• slight increase in spleen and bone marrow transitional B cells

abnormal plasma cell differentiation ( J:130897 )

• reduced plasma cell generation

decreased immunoglobulin level ( J:130897 )

decreased IgG level ( J:130897 )

• non-statistical reductions in IgG response to particulate antigens

decreased IgG1 level ( J:130897 )

decreased IgG2a level ( J:130897 )

decreased IgG2c level ( J:130897 )

decreased IgM level ( J:130897 )

• response to particulate antigens is reduced to 65% of normal at 7 days

Genotype
MGI:4888253

hm2

• Allelic Composition: Cd36^tm1Mfe/Cd36^tm1Mfe
• Genetic Background: involves: 129S1/Sv

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:220343 )

N • fasted mice at room temperature and exposed to cold exhibit normal serum levels of non-esterified fatty acids and ketone bodies

impaired adaptive thermogenesis ( J:220343 )

• fasted mice exposed to cold exhibit a rapid drop in body temperature compared with wild-type mice

• however, fed mice exhibit normal body temperature when cold exposed

decreased circulating glucose level ( J:220343 )

• in fasted mice at room temperature and exposed to cold

decreased skeletal muscle glycogen level ( J:220343 )

• in fasted mice at room temperature and more pronounced when mice are exposed to cold

abnormal triglyceride level ( J:220343 )

• reduced triglyceride levels in brown adipose tissue in fasted mice at room temperature and more pronounced when mice are exposed to cold

decreased circulating triglyceride level ( J:220343 )

• in fasted mice at room temperature and more so in fasted mice exposed to cold

adipose tissue

decreased brown adipose tissue amount ( J:220343 )

• in fasted mice at room temperature and exposed to cold

decreased adipocyte glucose uptake ( J:220343 )

• reduced glucose uptake in the brown adipose tissue of fasted mice exposed to cold

abnormal brown adipose tissue physiology ( J:220343 )

• reduced glucose uptake in the brown adipose tissue of fasted mice exposed to cold

• reduced fatty acid uptake in the brown adipose tissue of fasted mice at room temperature and exposed to cold

nervous system

abnormal myelination ( J:89664 )

• more thinly myelinated fibers are found at 3 and 6 weeks after sciatic nerve crush injury than in controls

• myelinated fibers with decreased diameters

abnormal peripheral nervous system regeneration ( J:89664 )

• more thinly myelinated fibers are found at 3 and 6 weeks after sciatic nerve crush injury than in controls

• myelinated fibers with decreased diameters

• more macrophage present

immune system

abnormal macrophage chemotaxis ( J:89664 )

• more macrophage present at 3 and 6 weeks after sciatic nerve crush injury than in controls

muscle

decreased skeletal muscle glycogen level ( J:220343 )

• in fasted mice at room temperature and more pronounced when mice are exposed to cold

abnormal muscle physiology ( J:220343 )

• glucose uptake in skeletal muscles is not enhanced by cold-exposure in fasted mice

• reduced fatty acid uptake in skeletal muscles at room temperature and in cold-exposed fasted mice

decreased muscle cell glucose uptake ( J:220343 )

• glucose uptake in skeletal muscles is not enhanced by cold-exposure in fasted mice

cardiovascular system

abnormal blood pressure regulation ( J:109739 )

• resting coronary resistance is lower than in controls

• hexarelin fails to induce a dose dependent increase in coronary perfusion pressure as it does in controls

cellular

decreased adipocyte glucose uptake ( J:220343 )

• reduced glucose uptake in the brown adipose tissue of fasted mice exposed to cold

abnormal macrophage chemotaxis ( J:89664 )

• more macrophage present at 3 and 6 weeks after sciatic nerve crush injury than in controls

decreased muscle cell glucose uptake ( J:220343 )

• glucose uptake in skeletal muscles is not enhanced by cold-exposure in fasted mice

hematopoietic system

abnormal macrophage chemotaxis ( J:89664 )

• more macrophage present at 3 and 6 weeks after sciatic nerve crush injury than in controls

Genotype
MGI:3587412

hm3

• Allelic Composition: Cd36^tm1Mfe/Cd36^tm1Mfe
• Genetic Background: involves: 129S1/Sv * C57BL/6

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:123605 )

N • glycogen synthesis is normal

abnormal response to cardiac infarction ( J:83611 , J:112746 )

• exhibit a significant reduction in tolerance to ischemia; cardiac output is significantly lower and end-diastolic pressure is significantly higher after ischemia, regardless of whether the perfusate is with or without fatty acids, compared to controls (J:83611)

• survival of hearts is lower (53%) than that of wild-type (80%) after a 6-min ischemic insult (J:83611)

• recovery after ischemia is similar to controls in another study which also saw no adverse effect on survival (J:112746)

abnormal homeostasis ( J:123605 )

decreased cardiac muscle glycogen level ( J:83611 )

• decrease in glycogen levels in the heart

decreased fasting circulating glucose level ( J:56081 )

• lower fasting glucose levels

abnormal hormone level ( J:126461 )

increased circulating leptin level ( J:126461 )

• plasma levels are 2 fold higher than for controls, even when fasted

• increased leptin mRNA in adipocytes

• leptin response to intragastric glucose administration is strongly enhanced and persists at least 4 hours

decreased circulating adiponectin level ( J:126461 )

• blood levels are decreased

abnormal lipid homeostasis ( J:56081 )

• the uptake of oleate, a long chain fatty acid, by adipoctyes is reduced at low fatty acid:BSA ratios, indicating the absence of high affinity uptake in these cells

• adipocytes exhibit an increased incorporation of palmitate into diacylglycerol

• elicited peritoneal macrophages exhibit a 40-47% decrease in binding of oxidized LDL at saturation and a 63% decrease in cell association

abnormal intestinal lipid absorption ( J:123605 )

• 50% reduction in oleic acid uptake in the first third of the small intestine

• also reduced uptake in the middle third but not in the distal third

• reduced incorporation of fatty acids into triglycerides in the first third of the small intestine

• decreased secretion of newly synthesized triglycerides in the first third but not the remainder of the small intestine

decreased intestinal cholesterol absorption ( J:123605 )

• more cholesterol retained in the intestinal lumen

• 50% reduction in cholesterol output to lymph

• cholesterol uptake in the first third of the small intestine is reduced more than 60%

• no defect in cholesterol uptake in the distal two-thirds of the small intestine

increased circulating ketone body level ( J:126461 )

• plasma beta hydroxybutyrate levels are increased

abnormal cholesterol homeostasis ( J:56081 )

• high density lipoprotein (HDL) particles are larger and contain increased phospholipid

increased circulating cholesterol level ( J:56081 )

• higher fasting and nonfasting levels of cholesterol

increased circulating HDL cholesterol level ( J:56081 )

• increase in cholesterol level is mainly due to an increase in the HDL fraction

increased fatty acids level ( J:56081 )

• higher fasting levels of nonesterified free fatty acids

abnormal triglyceride level ( J:123605 )

• reduced incorporation of glucose into triglycerides

decreased cardiac muscle triglyceride level ( J:83611 )

• decrease in triglyceride levels in the heart

increased circulating triglyceride level ( J:56081 )

• higher fasting levels of triacylglycerol, mainly within the very low density lipoprotein fraction

increased circulating VLDL triglyceride level ( J:56081 )

abnormal basal metabolism ( J:126461 )

• unadjusted metabolic rate is reduced by 15%

• rate adjusted to body weight is normal

cardiovascular system

decreased cardiac muscle glycogen level ( J:83611 )

• decrease in glycogen levels in the heart

decreased cardiac muscle triglyceride level ( J:83611 )

• decrease in triglyceride levels in the heart

cardiac hypertrophy ( J:83611 )

• increase in the heart/body weight ratio, although exhibit no significant differences in body and heart weights

abnormal cardiovascular system physiology ( J:83611 , J:112746 )

• heart exhibits a significant decrease in palmitate oxidation and ATP levels, however cardiac output and end-diastolic pressure is normal under nonischemic conditions (J:83611)

• lower palmitate oxidation rates relative to controls offset by increased glucose oxidation levels with normal ATP production in another study (J:112746)

• cardiac work in non-ischemic hearts elevated relative to controls in another study (J:112746)

increased cardiac muscle cell glucose uptake ( J:83611 )

• increase in glucose uptake in the heart

abnormal response to cardiac infarction ( J:83611 , J:112746 )

• exhibit a significant reduction in tolerance to ischemia; cardiac output is significantly lower and end-diastolic pressure is significantly higher after ischemia, regardless of whether the perfusate is with or without fatty acids, compared to controls (J:83611)

• survival of hearts is lower (53%) than that of wild-type (80%) after a 6-min ischemic insult (J:83611)

• recovery after ischemia is similar to controls in another study which also saw no adverse effect on survival (J:112746)

muscle

decreased cardiac muscle glycogen level ( J:83611 )

• decrease in glycogen levels in the heart

decreased cardiac muscle triglyceride level ( J:83611 )

• decrease in triglyceride levels in the heart

increased cardiac muscle cell glucose uptake ( J:83611 )

• increase in glucose uptake in the heart

growth/size/body

cardiac hypertrophy ( J:83611 )

• increase in the heart/body weight ratio, although exhibit no significant differences in body and heart weights

decreased body size ( J:123605 , J:126461 )

• body size smaller than in controls (J:123605)

• weight difference from controls significant after 12 weeks of age (J:126461)

slow postnatal weight gain ( J:126461 )

• gain less weight than controls

• weight difference from controls significant after 12 weeks of age

digestive/alimentary system

abnormal small intestine morphology ( J:123605 )

• small intestine is longer than in controls

abnormal intestinal absorption ( J:123605 )

increased intestinal glucose absorption ( J:123605 )

• increased glucose uptake rate in the first third of the small intestine

abnormal intestinal lipid absorption ( J:123605 )

• 50% reduction in oleic acid uptake in the first third of the small intestine

• also reduced uptake in the middle third but not in the distal third

• reduced incorporation of fatty acids into triglycerides in the first third of the small intestine

• decreased secretion of newly synthesized triglycerides in the first third but not the remainder of the small intestine

decreased intestinal cholesterol absorption ( J:123605 )

• more cholesterol retained in the intestinal lumen

• 50% reduction in cholesterol output to lymph

• cholesterol uptake in the first third of the small intestine is reduced more than 60%

• no defect in cholesterol uptake in the distal two-thirds of the small intestine

adipose tissue

abnormal fat pad morphology ( J:126461 )

• epididymal fat pads weigh less than in controls

decreased percent body fat/body weight ( J:126461 )

• total body fat about 38% lower than in controls

• lean mass normal

skeleton

decreased bone mass ( J:126461 )

• significantly reduced bone mass

behavior/neurological

abnormal food intake ( J:126461 )

• food intake reduced 20%

cellular

increased cardiac muscle cell glucose uptake ( J:83611 )

• increase in glucose uptake in the heart

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
platelet-type bleeding disorder 10		DOID:0111046	OMIM:608404	J:56081

Genotype
MGI:4888254

cx4

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Cd36^tm1Mfe/Cd36^tm1Mfe
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6

homeostasis/metabolism

abnormal lipid level ( J:61672 )

decreased circulating triglyceride level ( J:61672 )

• females with reduced triacyl glycerol on a high fat diet

increased cholesterol level ( J:61672 )

• females with higher cholesterol levels on a normal fat diet

xanthoma ( J:61672 )

• more subcutaneous xanthomas than found when Apoe^tm1Unc is alone

cardiovascular system

decreased susceptibility to atherosclerosis ( J:61672 )

• lesions 45% smaller in size in males and mostly restricted to the aortic arch rather than throughout the aortic tree

• 76% reduction in atherosclerotic lesions in the aorta when on a high fat diet as compared to Apoe^tm1Unc

• area covered by lesions is 5% as compared to 30% in Apoe^tm1Unc homozygous males

• female lesions closer in size to Apoe^tm1Unc controls

• smaller lesions on a low fat diet as well and also for females

• lesions composed of more densely packed lipid laden foam cells

growth/size/body

increased growth rate ( J:61672 )

• gain significantly more weight on a high fat diet than Apoe^tm1Unc controls

• on a normal diet only males are significantly heavier than controls

immune system

abnormal macrophage derived foam cell morphology ( J:61672 )

• less foam cell development

abnormal macrophage physiology ( J:61672 )

• considerably less modified LDL is bound and cellular uptake is reduced

• native LDL binding is normal

cellular

abnormal macrophage derived foam cell morphology ( J:61672 )

• less foam cell development

hematopoietic system

abnormal macrophage derived foam cell morphology ( J:61672 )

• less foam cell development

abnormal macrophage physiology ( J:61672 )

• considerably less modified LDL is bound and cellular uptake is reduced

• native LDL binding is normal