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Allele Symbol Allele Name Allele ID |
Lrp1tm2Her targeted mutation 2, Joachim Herz MGI:2180880 |
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| Summary |
18 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• impaired ability to clear 125I-labeled alpha2-macroglobulin from the plasma after adenoviral cre injection into the liver
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| N |
• unlike in double mutant mice that are also null for Ldlr , adenoviral cre infection does not alter circulating apolipoprotein levels or the plasma cholesterol profile
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• medial thickness is doubled with an increase in the number of cell nuclei
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• increase in the number of disruptions of the elastic layers
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• freshly isolated cells are more epithelioid shaped compared to the spindled shaped cells from control mice
• alpha-actin filaments are less abundant and often disrupted in quiescent smooth muscle cells
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• aortic smooth muscle cells challenged with PDGF-bb display more rapid alpha-actin filament disassembly and fillapodial extension and enhanced proliferation and migration compared to controls
• cultured aortic smooth muscle cells show enhanced serum induced cell growth
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• aortic rings mice fail to reach the 50% level of force generation at any concentration of KCl and phenylephrine tested
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• increase in neointimal formation and prolonged neointimal hyperplasia following endothelial denudation of carotid arteries
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• increase in neointimal formation and prolonged neointimal hyperplasia following endothelial denudation of carotid arteries
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• freshly isolated cells are more epithelioid shaped compared to the spindled shaped cells from control mice
• alpha-actin filaments are less abundant and often disrupted in quiescent smooth muscle cells
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• aortic smooth muscle cells challenged with PDGF-bb display more rapid alpha-actin filament disassembly and fillapodial extension and enhanced proliferation and migration compared to controls
• cultured aortic smooth muscle cells show enhanced serum induced cell growth
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• aortic rings mice fail to reach the 50% level of force generation at any concentration of KCl and phenylephrine tested
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• impaired ability to internalize targets coated with LRP ligands
• however, phagocytosis of apoptotic cells in serum free conditions is similar to controls
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• impaired ability to internalize targets coated with LRP ligands
• however, phagocytosis of apoptotic cells in serum free conditions is similar to controls
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• impaired ability to internalize targets coated with LRP ligands
• however, phagocytosis of apoptotic cells in serum free conditions is similar to controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• the total macrophage and collagen lesion contents are increased
• the percentage (normalized for lesion size) of collagen in lesions is increased; however, the percentages of macrophages and smooth muscle cells in the lesions are similar
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• total atherosclerotic lesion area and the proportion of advanced lesions are significantly increased compared to mutant mice expressing Lrp1
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion
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• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion
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• significant reduction in the accumulation of nitrotyrosine in the ischemic tissue
• treatment with PLAT fails to restore nitrotyrosine accumulation unlike in mice null for Plat
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• 24 hours after transient middle cerebral artery occlusion
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• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion
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• significant reduction in the accumulation of nitrotyrosine in the ischemic tissue
• treatment with PLAT fails to restore nitrotyrosine accumulation unlike in mice null for Plat
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• 24 hours after transient middle cerebral artery occlusion
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• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion
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• significant decrease in the number of activated glial cells in ischemic tissue after transient middle cerebral artery occlusion
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• after adenoviral cre infection
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• after adenoviral cre infection, concentrations of apoB48 are dramatically increased
• this increase is primarily responsible for the increase in plasma cholesterol and triglyceride levels
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• slightly increased after adenoviral cre infection
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• after adenoviral cre infection, the total cholesterol profile is dramatically changed
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• increase in total plasma cholesterol levels after adenoviral cre infection
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• large increase of plasma lipoproteins in the LDL size range after adenoviral cre infection
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• large increase of plasma lipoproteins in the chylomicron remnant/VLDL size range after adenoviral cre infection
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in the cortex of the brain at 12 months of age
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• decrease in spine densities of apical oblique and basal shaft dendrites of pyramidal neurons in the cortex and in the CA1 region of the hippocampus at 18 months but not at 12 months of age
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• expression analysis indicates an age dependent decrease in synaptic density
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• significant increase in apoptotic cells in the cortex and hippocampus at 24 months but not at 18 months of age
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• significantly lower levels of sulfatide, galactosylceramide, cholesterol and triglyceride in the cortex of the brain at 12 months of age
• amyloid-beta levels are decreased in the hippocampus at 18 months of age, indicating that the neurodegeneration likely occurs by an amyloid-beta independent mechanism
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• increase in reactive astrocytes and microglial activation in the CA1 region of the hippocampus and in the dentate gyrus but not in the CA3 region of the hippocampus at 18 months of age
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• severely reduced in hippocampal slices at 18 months of age
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• exhibit significantly less freezing time than controls at 18 months of age
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• exhibit significantly less freezing time than controls at 18 months of age
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• develops by 13 months of age
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• at 18 months of age
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• in an open field test at 18 months of age
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• significantly lower levels of sulfatide and galactosylceramide in the cortex of the brain at 12 months of age
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• in the cortex of the brain at 12 months of age
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• in the cortex of the brain at 12 months of age
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• increase in reactive astrocytes and microglial activation in the CA1 region of the hippocampus and in the dentate gyrus but not in the CA3 region of the hippocampus at 18 months of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Alzheimer's disease | DOID:10652 | J:167724 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• amyloid beta deposition in the brains is higher than in controls with only Tg(PSEN1)5Dbo and Tg(APP69ff5)3Dbo at 13-14 months of age
• amyloid beta deposition is seen in the cortical parenchyma and in cortical vessels as cerebral amyloid angiopathy
• concentrations of insoluble amyloid beta40 and amyloid beta42 is higher than in controls at 13-14 months of age but not at 3 months
• despite the increase in amyloid beta deposition, APP processing and levels of amyloid beta degrading enzymes are normal, indicating that the increase is due to a disturbance of lysosomal-mediated amyloid beta clearance
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• amyloid beta deposition is seen in cortical vessels as cerebral amyloid angiopathy
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• activation of astrocytes is enhanced compared to controls with only Tg(PSEN1)5Dbo and Tg(APP69ff5)3Dbo at 1 year of age
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• amyloid beta deposition in the brains is higher than in controls with only Tg(PSEN1)5Dbo and Tg(APP69ff5)3Dbo at 13-14 months of age
• amyloid beta deposition is seen in the cortical parenchyma and in cortical vessels as cerebral amyloid angiopathy
• concentrations of insoluble amyloid beta40 and amyloid beta42 is higher than in controls at 13-14 months of age but not at 3 months
• despite the increase in amyloid beta deposition, APP processing and levels of amyloid beta degrading enzymes are normal, indicating that the increase is due to a disturbance of lysosomal-mediated amyloid beta clearance
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• amyloid beta deposition is seen in cortical vessels as cerebral amyloid angiopathy
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Alzheimer's disease | DOID:10652 | J:192453 | ||
| cerebral amyloid angiopathy | DOID:9246 | J:192453 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced by more than 65% compared to controls
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• difference in body weight is entirely due to the decrease in fat mass
• due to a macroscopically obvious decrease in the interscapular and epididymal fat pads
• increase in fat mass loss when fasted for 24 h
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• dramatic decrease in uptake of lipids by adipocytes
• decrease is more dramatic in brown adipose tissue compared to white adipose tissue
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• when placed on a high fat diet
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• increase in fat mass loss when fasted for 24 h
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| N |
• no difference in respiratory quotients is detected compared to controls
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• core temperature decreases faster when the ambient temperature is lowered compared to similarly exposed controls
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• consistent with the decrease in total body fat amount
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• at 22 degrees C core temperature is similar to controls but surface temperature is reduced
• the difference in surface temperature compared to controls becomes more pronounced at 4 degrees C
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• behavioral signs (shivering and trunk curl) indicate impaired ability to maintain body temperature
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• on normal chow and high fat diets
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• when placed on a high fat diet
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• markedly lower fasting glucose levels
• fasting glucose levels do not increase even after 16 weeks on a high fat diet
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• markedly lower fasting insulin levels
• fasting insulin levels do not increase even after 16 weeks on a high fat diet
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• results indicate that skeletal muscle is responsible for the elevated plasma glucose clearance
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• postprandial lipid clearance from the circulation in response to a bolus fat load is markedly delayed
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• markedly lower fasting non-esterified fatty acids levels
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• despite weighing less, mice consume more food compared to controls
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• body surface reduction by coiling up that is visible at room temperature (22 degrees C) but becomes more pronounced at 4 degrees C
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• enhanced skeletal muscle glucose uptake consistent with the increased muscle activity is seen
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• enhanced skeletal muscle glucose uptake consistent with the increased muscle activity is seen
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• die around 9 months of age
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• greatly reduced fertility
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• adults eat more compared to wild-type controls
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• mild
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• develop dystonic posturing over time
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• over time increased plantar flexion of the feet occurs, with asymmetric involvement in some mice
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• waddling gait
• step width increases in relation to step length
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• general hyperactivity combined with increased voluntary movement, detectable by 3 weeks of age
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• initially similar in size and weight to wild-type controls but gradually fall behind in their growth rate
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• adults are leaner than wild-type controls
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| N |
• no histological defects in brain morphology are detected
• electroencephalographic and electromyographic studies confirmed the tremor but did not detect any abnormalities in neuro- or neuromuscular transmission
• no abnormalities in hippocampal long term potentiation are detected
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• following pIpC treatment, plasma cholesterol level is lower compared to mutant mice wild-type for Lrp1
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• following pIpC treatment, plasma LDL cholesterol level is lower compared to mutant mice wild-type for Lrp1
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• following pIpC treatment, plasma VLDL cholesterol level is lower compared to mutant mice wild-type for Lrp1
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• following pIpC treatment, plasma triglyceride level is lower compared to mutant mice wild-type for Lrp1
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• increase in tissue type plasminogen activator levels by 4 weeks after pIpC treatment
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• following pIpC treatment, plasma lipoprotein lipase level is higher compared to mutant mice wild-type for Lrp1
• however, no increase in lipoprotein lipase activity is detected
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• increase in Factor VIII levels by 4 weeks after pIpC treatment
(J:90547)
• mice show elevated FVIII (Factor 8) levels
(J:117317)
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• increase in von Willebrand factor levels by 4 weeks after pIpC treatment
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• increase in lesion size in pIpC treated mice compared to untreated controls
• however, no change in lesion composition is detected
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• grossly disrupted
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• progressive thickening of the aorta wall with age
• thickening is primarily caused by increased smooth muscle cell proliferation
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• aortas are consistently distended and dilated
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• pronounced atherosclerosis is seen in the aorta
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• on a high cholesterol diet
• addition of Gleevec to the diet protects against atherosclerotic lesion formation
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• almost complete occlusion of the mesenteric arteries
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• increase in vascular smooth muscle cell proliferation
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• increase in vascular smooth muscle cell proliferation
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| N |
• no changes in cholesterol or triglyceride levels are detected compared to mice homozygous for Ldlrtm1Her alone
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• increase in vascular smooth muscle cell proliferation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increase in total plasma cholesterol levels within 10 days of pIpC injection
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• large increase of plasma lipoproteins in the LDL size range within 10 days of pIpC injection
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• large increase of plasma lipoproteins in the chylomicron remnant/VLDL size range within 10 days of pIpC injection
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• within 10 days of pIpC injection
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• within 10 days of pIpC injection, concentrations of apoB48 are dramatically increased
• this increase is primarily responsible for the increase in plasma cholesterol and triglyceride levels
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• clearance of Factor VII from the plasma is slower in pIpC treated mice
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• increase in Factor VIII levels by 10 days after pIpC treatment
• increase in levels persists for at least 6 weeks after pIpC treatment
• the ratio of Factor VIII to von Willebrand factor is also increased following pIpC treatment
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• increase in von Willebrand factor levels by 10 days after pIpC treatment
• increase in levels persists for at least 6 weeks after pIpC treatment
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• clearance of Factor VII from the plasma is slower in pIpC treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice show significantly elevated FVIII (Factor 8), similar to Ldlr/Lrp double mutants
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• ascending aortas are characterized by increased cell nuclei and fractured elastic laminae and show progressive intra-lamellar thickening, extracellular matrix deposition, and cellular disorganization
• medial layers of the ascending aorta exhibits increased cellular and intracellular accumulation of connective tissue growth factor
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• dilated ascending aortas in mice older than 36 weeks of age
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• dilation of aortic roots is seen beginning at 16 weeks of age and progresses with age
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• coronary arteries within the left ventricle show accumulation of collagen within the tunica media and adventitia
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• increase in perivascular fibrosis with outward extension of fibrotic lesions surrounding intramural coronary arteries in 48 week old mice
• extensive and continuous fibrotic lesions tracts extending outward from coronary arteries are sporadically seen in ventricle walls
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• increase in myocyte longitudinal area in parenchymal regions of the left ventricle free wall in 48 week old mice
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• increase in heart size in mice older than 36 weeks of age
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• heart weight to body weight ratios are increased throughout the age range from 16 to 70 weeks of age
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• left ventricle enlargement in 48 week old mice
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• interstitial fibrosis in intramural coronary arteries of left ventricle free wall and extensive fibrosis in left ventricle papillary muscles
• however, no pericellular fibrosis is seen
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• a 38% reduction in fractional shortening and 43% reduction in ejection fraction
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• echocardiography shows a reduction in systolic function, with a 38% reduction in fractional shortening, 43% reduction in ejection fraction, and 68% increase in left ventricular diameter in 36 week old mice
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• mice show age-dependent increase in incidence of aortic insufficiency, with all mice showing it at 30 weeks of age
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• 24 week old mice exhibit a 44% higher pulse pressure than controls
• captopril treatment reduces pulse pressure to levels seen in untreated control mice
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• 16% reduction in diastolic pressure in 24 week old mice
• however, systolic blood pressure is normal
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• increase in myocyte longitudinal area in parenchymal regions of the left ventricle free wall in 48 week old mice
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• a 38% reduction in fractional shortening and 43% reduction in ejection fraction
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• increase in heart size in mice older than 36 weeks of age
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• heart weight to body weight ratios are increased throughout the age range from 16 to 70 weeks of age
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• interstitial fibrosis in intramural coronary arteries of left ventricle free wall and extensive fibrosis in left ventricle papillary muscles
• however, no pericellular fibrosis is seen
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| cardiomyopathy | DOID:0050700 | J:209752 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• cholesterol levels are significantly increased (>10-fold) compared to controls
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• triglyceride levels are significantly increased (>10-fold) compared to controls
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• FVIII levels are increased by 4.2-fold compared to controls
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• von Willebrand factor levels are increased by 3.3-fold compared to controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tissue plasminogen activator (t-PA) levels are increased by 2.4-fold relative to controls
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• FVIII levels are slightly elevated by 1.6-fold relative to controls
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• von Willebrand factor levels are sligthly elevated by 1.3-fold relative to controls
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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 04/16/2024 MGI 6.23 |
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