Phenotypes Associated with This Genotype

Genotype
MGI:3772339

• Allelic Composition: Ldlr^tm1Her/Ldlr^tm1Her
• Genetic Background: B6.129S7-Ldlr^tm1Her

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

Adiposity in Ldlr^tm1Her/Ldlr^tm1Her and Scd1^ab-2J/Scd1^ab-2J Ldlr^tm1Her/Ldlr^tm1Her mice

homeostasis/metabolism

amyloid beta deposits ( J:137264 )

• increased amyloid beta 40 but not amyloid beta 42 on a high fat diet

hyperglycemia ( J:100916 , J:130278 )

• streptozotocin (STZ) treatment leads to 3-fold higher level of blood glucose in mice fed a high fat diet (J:100916)

• these high glucose levels persist for at least 12 weeks after STZ treatment (J:100916)

• when fed a western style diet for 12 weeks (J:130278)

increased circulating insulin level ( J:130278 )

• when fed a western style diet for 12 weeks

abnormal circulating cholesterol level ( J:100916 , J:130278 )

• streptozotocin (STZ) induced diabetes leads to blood cholesterol levels that are twice those of non-diabetic mice 6 weeks post-induction and three times greater 8 weeks post- induction (J:100916)

• when fed a western style diet for 12 weeks, male mice exhibit a higher circulating cholesterol level than in Ldlr^tm1Her Scd1^ab-2J homozygotes (J:130278)

decreased circulating HDL cholesterol level ( J:130794 )

• when fed a high-cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for HDL of 0.77 compared to 0.83 in wild-type mice

increased circulating cholesterol level ( J:61287 , J:72027 , J:135078 , J:137264 )

• mice develop severe cholesterolemia when receiving a high fat diet from 6 to 30 weeks (elevated levels are detected at 6, 15, and 30 weeks) (J:61287)

• seen at 3-4 months of age (J:72027)

• 10 fold increase in total cholesterol on a high fat diet compared to a 150% increase for controls (J:137264)

• 3 fold cholesterol elevation on a normal diet relative to controls (J:137264)

increased circulating HDL cholesterol level ( J:72027 )

• slightly elevated at 3 and 8 months of age

increased circulating LDL cholesterol level ( J:72027 , J:130794 )

• when fed a high cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for LDL of 0.88 compared to 0.84 in wild-type mice (J:130794)

increased circulating VLDL cholesterol level ( J:130278 , J:130794 )

• compared to in Ldlr^tm1Her Scd1^ab-2J homozygotes when fed a western style diet for 12 weeks (J:130278)

• when fed a high cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for VLDL of 0.92 compared to 0.88 in wild-type mice (J:130794)

increased circulating interleukin-1 beta level ( J:137264 )

decreased circulating interleukin-10 level ( J:130794 )

increased circulating interleukin-6 level ( J:137264 )

increased circulating tumor necrosis factor level ( J:137264 )

• increased TNFalpha levels

impaired glucose tolerance ( J:130278 )

• when fed a western style diet for 12 weeks

increased liver cholesterol level ( J:72027 )

• livers exhibit slightly, but significantly, higher levels of cholesterol

abnormal triglyceride level ( J:130278 )

increased circulating triglyceride level ( J:72027 , J:130278 , J:137264 )

• seen at 3-4 months of age (J:72027)

• when fed a western style diet for 12 weeks, female mice exhibit a higher circulating triglyceride level than in Ldlr^tm1Her Scd1^ab-2J homozygotes (J:130278)

• elevated on a high fat diet (J:137264)

increased circulating VLDL triglyceride level ( J:130278 )

• compared to in Ldlr^tm1Her Scd1^ab-2J homozygotes when fed a western style diet for 12 weeks

increased liver triglyceride level ( J:130278 )

• when fed a western style diet for 12 weeks, mice exhibit a 5-fold higher hepatic triglyceride level than in Ldlr^tm1Her Scd1^ab-2J homozygotes

adipose tissue

abnormal fat pad morphology ( J:130278 )

• increased when fed a western style diet for 12 weeks

increased percent body fat/body weight ( J:130278 )

• when fed a western style diet for 12 weeks

growth/size/body

decreased susceptibility to weight gain ( J:135078 )

• lower body weight on a low cholesterol diet than controls on any diet

increased susceptibility to weight gain ( J:130278 )

• when fed a western style diet for 12 weeks

cardiovascular system

atherosclerotic lesions ( J:61287 , J:110061 )

increased susceptibility to atherosclerosis ( J:100916 , J:110061 , J:130794 , J:135078 )

• high-fat diet leads to atherosclerosis (J:100916)

• STZ-induced diabetes leads to an almost 3-fold greater size in total lesion area in the aorta compared to non-diabetic Ldlr ^tm1Her homozyogotes (J:100916)

• 4 weeks on the Western diet mice have lesions of small fatty streaks on the aorta (J:110061)

• after 12 weeks on a high cholesterol diet, mice exhibit extensive intimal thickening and 60% to 80% of the aortic surface is sudanophilic unlike in wild-type mice (J:130794)

• after 12 weeks on a high cholesterol diet, mice exhibit endothelial disruption and an accumulation of macrophage and foam cells at the site of atherosclerotic plaques (J:130794)

immune system

abnormal microglial cell morphology ( J:137264 )

• increased number of microglia in the hippocampus

increased circulating interleukin-1 beta level ( J:137264 )

decreased circulating interleukin-10 level ( J:130794 )

increased circulating interleukin-6 level ( J:137264 )

increased circulating tumor necrosis factor level ( J:137264 )

• increased TNFalpha levels

liver/biliary system

increased liver cholesterol level ( J:72027 )

• livers exhibit slightly, but significantly, higher levels of cholesterol

increased liver triglyceride level ( J:130278 )

• when fed a western style diet for 12 weeks, mice exhibit a 5-fold higher hepatic triglyceride level than in Ldlr^tm1Her Scd1^ab-2J homozygotes

hepatic steatosis ( J:130278 )

• when fed a western style diet for 12 weeks

behavior/neurological

abnormal spatial learning ( J:135078 )

• take longer to reach the target site in a Morris water maze when fed a high cholesterol diet

impaired spatial working memory ( J:137264 )

• deficient performance in a water radial arm maze regardless of the diet

increased grip strength ( J:135078 )

• perform better than controls on a hanging bar test

increased locomotor activity ( J:135078 )

• travel greater distances and spend more time in motion in an open field test

nervous system

abnormal CNS glial cell morphology ( J:137264 )

abnormal astrocyte morphology ( J:137264 )

• increased numbers of reactive astrocytes

• further increase in reactive astrocytes on a high fat diet

abnormal microglial cell morphology ( J:137264 )

• increased number of microglia in the hippocampus

amyloid beta deposits ( J:137264 )

• increased amyloid beta 40 but not amyloid beta 42 on a high fat diet

hematopoietic system

abnormal microglial cell morphology ( J:137264 )

• increased number of microglia in the hippocampus

cellular

abnormal CNS glial cell morphology ( J:137264 )

abnormal astrocyte morphology ( J:137264 )

• increased numbers of reactive astrocytes

• further increase in reactive astrocytes on a high fat diet

abnormal microglial cell morphology ( J:137264 )

• increased number of microglia in the hippocampus