Analysis Tools
homeostasis/metabolism
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Allele Symbol Allele Name Allele ID |
Apobtm2Sgy targeted mutation 2, Stephen G Young MGI:1857304 |
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| Summary |
9 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 12 weeks of age, atherosclerotic lesions are seen mainly in the aortic region of the whole aorta
• leptin treatment, but not food restriction, results in lower atherosclerotic lesion size
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• elevated blood pressure
• treatment with enalapril corrects the elevated blood pressure
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• increase in body weight, with mice weighing about 63 grams at 15-16 weeks of age
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• mice are hyperglycemic and glycemic control fluctuates with age
• mice show improved in blood glucose with food restriction but not with leptin treatment
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• increase in blood insulin levels
• neither food restriction or leptin treatment has an effect on insulin level
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• mice have higher VLDL levels than LDL, with lower HDL levels compared to wild-type mice which have HDL as the dominant lipoprotein species and very low levels of LDL and VLDL
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• mice have lower HDL levels
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• cholesterol levels are elevated almost 10-fold compared to wild-type mice
• both leptin treatment and food restriction result in 52.6% and nonsignificant 18.5% reduction, respectively, of cholesterol levels
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• mice have higher VLDL levels than LDL levels
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• plasma triglyceride levels are 4-fold higher at 15-16 weeks of age than in wild-type mice
• neither food restriction or leptin treatment has an effect on plasma triglyceride levels
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• glucose intolerance is evident at 7-8 weeks of age and sustained until 15-16 weeks
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| abdominal obesity-metabolic syndrome 1 | DOID:14221 |
OMIM:605552 |
J:133453 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit fewer atherosclerotic lesions in aortas and smaller lesions in the aortic root than single Apoetm1Unc homozygotes
• extent of atherosclerosis correlates with plasma cholesterol levels
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• mice are slightly, but significantly lighter than single Apoetm1Unc homozygotes at 200 days of age
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• triglyceride levels are higher than in single Apoetm1Unc homozygotes
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• the VLDL is more enriched in triglyceride than the VLDL from double Apobtm1Sgy Apoetm1Unc homozygotes
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• mean size of VLDL is larger than that of the VLDL from single Apoetm1Unc homozygotes or double Apobtm1Sgy Apoetm1Unc homozygotes
• the IDL and LDL particles are larger than that from single Apoetm1Unc homozygotes or double Apobtm1Sgy Apoetm1Unc homozygotes
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• HDL cholesterol levels at 200 days of age are slightly, but significantly, higher than in single Apoetm1Unc homozygotes or double Apobtm1Sgy Apoetm1Unc homozygotes
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• very high levels of VLDL cholesterol
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• total cholesterol levels are lower at 7 weeks, 3 and 6 months, and 200 days of age compared to single Apoetm1Unc homozygotes or double Apobtm1Sgy Apoetm1Unc homozygotes
• plasma cholesterol levels decrease with time
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• age related accumulation of esterified cholesterol in the basement of the retinal pigment epithelial layer
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• losses in rod and cone sensitivity only after 14 months of age
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• age related accumulation of esterified cholesterol in the basement of the retinal pigment epithelial layer
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 12 weeks of age, atherosclerotic lesions are seen mainly in the aortic region of the whole aorta
• leptin treatment and food restriction results in lower atherosclerotic lesion size
|
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• elevated blood pressure
• treatment with enalapril corrects the elevated blood pressure
|
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• increase in body weight, with mice weighing about 58 grams at 15-16 weeks of age
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• mice show increased insulin levels
• however, mice show normal glucose levels and glucose tolerance
• leptin treatment lowers insulin more than food restriction does
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• mice have more LDL than VLDL, with lower HDL levels compared to wild-type mice which have HDL as the dominant lipoprotein species and very low levels of LDL and VLDL
• both leptin treatment and food restriction result in 39.2% and 30% reduction, respectively, of cholesterol levels
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• mice have lower HDL levels
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• cholesterol levels are elevated almost 10-fold compared to wild-type mice
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• mice have more LDL than VLDL
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• plasma triglyceride levels are 3-fold higher at 15-16 weeks of age than in wild-type mice
• both leptin treatment and food restriction result in a 32% and 58%, respectively, reduction in circulating triglyceride levels
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| abdominal obesity-metabolic syndrome 1 | DOID:14221 |
OMIM:605552 |
J:133453 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• fasting glycemia is increased on a standard chow diet
• mice develop diabetes mellitus based on fasting hyperglycemia and lack of compensatory increase in insulin secretion when fed a high-fat/sucrose/cholesterol (HFSC) diet for 6 months
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• increase in fasting insulin levels on standard chow diet
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• mice exhibit cholesterolemia on both a standard chow diet and a high-fat/sucrose/cholesterol (HFSC) diet
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• mice fed the HFSC diet show higher expression of osteogenic genes in the aortic root
• mice fed the HFSC diet show aortic root fibrosis
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• HFSC-fed mice exhibit increased expression of hypertrophic cardiac markers
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• increase in left ventricular mass on both a chow and HFSC diet
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• left ventricular hypertrophy in HFSC-fed mice
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• mice fed the HFSC diet show aortic valve fibrosis
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• 80% of mice fed the HFSC diet for 6 months develop aortic stenosis, with mice showing increased peak aortic jet velocity, peak transvalvular pressure gradient, and mean transvalvular pressure gradient; magnitude of aortic stenosis is greater than in double Apob and Ldlr homozygotes
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• HFSC-fed mice exhibit aortic valve calcification
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• aortic valve area is decreased in HFSC-fed mice
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• total ventricular weight corrected for body weight is elevated in mice fed the HFSC diet
• when corrected for tibia length, the total ventricular weight is increased in mice either on the chow or HFSC diet
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• mice fed the HFSC diet show aortic root fibrosis and aortic valve fibrosis
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• echocardiography shows impaired left ventricular function in mice fed a chow diet with worsening cardiac dysfunction on the HFSC diet
• the mitral E/E ratio (mitral inflow measured by pulsed-wave over tissue Doppler) is increased in mice on the HFSC diet
• isovolumic relaxation time, corrected for heart rate, is decreased in mice on the HFSC diet
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• cardiac output is increased in mice fed the HFSC diet
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• stroke volume is increased in mice fed the HFSC diet
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• reduction in systolic fractional shortening in mice fed the HFSC diet
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• some areas of the aortic surface leaflet from HFSC-fed mice are denuded of endothelial cells and show presence of inflammatory cell aggregates, platelets, and fibrin covering the extracellular matrix
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• some areas of the aortic surface leaflet from HFSC-fed mice are denuded of endothelial cells and show presence of inflammatory cell aggregates, platelets, and fibrin covering the extracellular matrix
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• left ventricular hypertrophy in HFSC-fed mice
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• reduction in systolic fractional shortening in mice fed the HFSC diet
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• HFSC-fed mice exhibit increased expression of hypertrophic cardiac markers
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• left ventricular hypertrophy in HFSC-fed mice
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| aortic valve disease | DOID:62 | J:227165 | ||
| type 1 diabetes mellitus 2 | DOID:0110741 |
OMIM:125852 |
J:227165 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice fed the HFSC diet show higher expression of osteogenic genes in the aortic root
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• 40% of mice fed the HFSC diet for 6 months develop aortic stenosis, with mice showing increased peak aortic jet velocity, peak transvalvular pressure gradient, and mean transvalvular pressure gradient
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• total ventricular weight corrected for body weight is elevated in mice fed the HFSC diet
• however, when corrected for tibia length, the total ventricular weight is no longer elevated
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• cardiac output is increased in mice fed the HFSC diet
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• stroke volume is increased in mice fed the HFSC diet
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• reduction in systolic fractional shortening in mice fed the HFSC diet
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• increase in fasting insulin levels on standard chow diet
• however, mice show normal fasting glucose levels on standard chow diet
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• mice exhibit cholesterolemia on both a standard chow diet and a high-fat/sucrose/cholesterol (HFSC) diet
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• reduction in systolic fractional shortening in mice fed the HFSC diet
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• elevated relative to mice lacking the transgene at 6 months regardless of diet
• difference from controls lacking the transgene persists on a high fat diet but not on a normal diet at 15 months
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• plasma insulin levels are 2X control levels at 6 months in fed mice and fasted mice on a high fat diet
• fasted mice on a normal diet do not show elevated insulin
• reduced insulin sensitivity over the course of an insulin tolerance test
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• sustained elevation of blood glucose during a glucose tolerance test regardless of diet
• blood insulin is unchanged over the course of a glucose tolerance test
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• lesion thickness increases more on a high fat diet than does lesion area
• increased calcification of lesions after 15 months on a high fat diet, particularly for females
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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 04/30/2024 MGI 6.23 |
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