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Phenotypes Associated with This Genotype
Genotype
MGI:3611043
Allelic
Composition
Ldlrtm1Her/Ldlrtm1Her
Genetic
Background
involves: 129S7/SvEvBrd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ldlrtm1Her mutation (20 available); any Ldlr mutation (36 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• mice fed a diabetogenic high fat diet (35.5% carbohydrate and 36.6% fat) (DD diet) or a a diabetogenic high fat diet (35.5% carbohydrate and 36.6% fat) with 0.15% added cholesterol (DDC diet) exhibit weight gain leading to obesity; similar weight gain is seen regardless of diet

homeostasis/metabolism
• mothers on a high fat diet have reduced plasma concentrations of phenylalanine, lysine, valine, isoleucine, and leucine
• levels of other amino acids are normal
• levels in response to ACTH are significantly reduced
• similar levels of hypercholesterolemia are seen in mice fed the DD diet and those fed the DDC diet
• clearance of 125I-LDL from circulation is retarded, uptake of DiI-LDL by hepatocytes is decreased, and uptake of 3H-CE-LDL by the liver is lower compared to wild-type
• circulating fatty free acids are increased in mice fed the DD or the DDC diet, however levels are higher in the mice on the DDC diet
• similar levels of hypertriglyceridemia are seen in mice fed the DD diet and those fed the DDC diet
• ALT levels are increased in mice fed the DD diet and even more so in those fed the DDC diet
• increased fasting glucose levels after dexamethasone treatment
• after dexamethasone treatment
• glucose levels increase during a glucose tolerance test
• 30 minute insulin levels elevated
• less likely to become hypoglycemic during an insulin tolerance test
• hepatic cholesterol levels are increased only in the mice fed the DDC diet
• hepatic triglyceride levels are increased in mice fed the DD or the DDC diet, but higher in those on the DDC diet

nervous system
• on a Western diet, even small arterioles have associated microglia, sometimes within the basal lamina
• 2X as many arterioles have microglia
• reduced cell proliferation in the hippocampus
• reduced density of synaptophysin-immunoreactive presynaptic boutons in the CA1 of the hippocampus (J:120389)
• normal density of synaptophysin-immunoreactive presynaptic boutons in the dentate gyrus (J:120389)
• 32% of the cholesterol in the synaptic plasma membrane is in the exofacial leaflet as compared to 15% for controls
• cholesterol levels in the cytofacial leaflet are reduced
• cholesterol/phospholipid ratio in the synaptic plasma membrane is elevated
• fluidity of both the exofacial leaflet and the cytofacial leaflet of the synaptic plasma membrane are increased relative to controls

cardiovascular system
• wall thickness of brain arterioles having a lumen diameter of 15-40 um is greater than controls
• wall thickness increases on a Western diet
• wall thickness is directly related to the number of associated microglia
• thickened endothelial basal lamina
• reduced number of fenestrations
• narrowing of lumina

behavior/neurological
• mice on a Western diet fail to show improved performance over time in a Morris water maze test (J:116493)
• somewhat slower swimming speed in the acquisition phase of a Morris water maze test (J:120389)
• less time spent in the target quadrant during a probe test (J:120389)
• mice fed a Western diet and tested in a T-maze demonstrate reduced alternation returning more frequently to the blind arm of the maze (J:116493)

vision/eye
• thickened endothelial basal lamina
• reduced number of fenestrations
• narrowing of lumina
• decreased and irregular height
• basal membrane infoldings are less regular
• numerous vacuoles in cytoplasm
• thickened (up to 0.8um on a high fat diet)
• enhanced condensation of collagenous and elastic fibers
• laminations disrupted and large vacuoles become diffusely distributed

hematopoietic system
• on a Western diet, even small arterioles have associated microglia, sometimes within the basal lamina
• 2X as many arterioles have microglia

immune system
• on a Western diet, even small arterioles have associated microglia, sometimes within the basal lamina
• 2X as many arterioles have microglia
• inflammatory cell foci is seen to a greater extend in the livers of mice fed the DDC diet than the DD diet

pigmentation
• decreased and irregular height
• basal membrane infoldings are less regular
• numerous vacuoles in cytoplasm

cellular
• DD diet fed mice show some apoptotic cells in the liver while those on the DDC diet have a larger increase
• mice on the DDC diet exhibit an increase in hepatic oxidative stress
• poor survival of pups from mothers on a high fat diet
• intrauterine growth restriction of pups from mothers on a high fat diet
• also reduced birth weight persisting to at least 90 days of age
• offspring with lower gonadal fat pad to body weight ratio
• offspring with larger atherosclerotic lesions

liver/biliary system
• DD diet fed mice show some apoptotic cells in the liver while those on the DDC diet have a larger increase
• hepatic cholesterol levels are increased only in the mice fed the DDC diet
• hepatic triglyceride levels are increased in mice fed the DD or the DDC diet, but higher in those on the DDC diet
• inflammatory cell foci is seen to a greater extend in the livers of mice fed the DDC diet than the DD diet
• mice on the DD diet and on the DDC diet exhibit higher liver weights than regular chow-fed mice
• mice fed the DD diet exhibit diffuse macrovesicular steatosis with limited inflammation and fibrosis in the liver
• mice fed the DDC diet exhibit both macrovesicular and microvesicular steatosis in the liver
• intrasinusoidal and pericellular fibrosis is seen to a greater extend in the livers of mice fed the DDC diet than the DD diet


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
11/12/2019
MGI 6.14
The Jackson Laboratory