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Allele Symbol Allele Name Allele ID |
Irs3tm1Lhd targeted mutation 1, Gustav E Lienhard MGI:2149647 |
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| Summary |
2 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in general, homozygotes are viable, fertile and display normal growth and development as well as normal glucose homeostasis and normal insulin-stimulated glucose transport in adipocytes
• at 9-13 weeks of age, young male homozygotes show fasting plasma insulin levels that are 60% of wild-type levels; however, this difference is no longer apparent at 6 months
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• double mutant progeny are obtained at about half the expected frequency (3.4% vs. 6.25%), suggesting increased prenatal and/or early postnatal lethality
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• double homozygous males and females show severe growth retardation throughout life relative to wild-type mice
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• as early as 5 weeks, double homozygotes show increased blood glucose levels in both the fasted and the fed states
• notably, injection of leptin adenovirus leads to normalization of blood glucose levels in double mutant but not in wild-type mice
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• as early as 5 weeks, double homozygotes show increased plasma insulin levels in both the fasted and fed states
• notably, injection of leptin adenovirus leads to normalization of plasma insulin levels in double mutant but not in wild-type mice
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• in 2-month-old double homozygotes, fed plasma leptin levels are reduced relative to wild-type and single mutant mice; fasted plasma leptin levels are also reduced, albeit to a lesser extent than in the fed state
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• at 2 months, fasted plasma free fatty acid levels are significantly reduced in both male and female double homozygotes relative to wild-type mice, and in double homozygous males relative to Irs1tm1Jos and Irs3tm1Lhd mice
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• at 6 weeks, double homozygous males exhibit significant glucose intolerance
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• at 6 weeks, double homozygous males exhibit severe insulin resistance
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• in double homozygous males, whole-body triglyceride content is reduced by ~75%, ~45%, and ~70% relative to wild-type, Irs1tm1Jos, and Irs3tm1Lhd mice, respectively
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• at 2 months, fasted plasma triglyceride levels are markedly reduced in both male and female double homozygotes relative to wild-type and Irs3tm1Lhd mice, and in double homozygous females relative to Irs1tm1Jos mice
• although double mutant livers tend to contain less triglycerides than wild-type livers, this difference is statistically insignificant; skeletal muscle triglyceride content remains normal
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• in double homozygotes, perigonadal (white) fat pad mass is decreased by ~95%, ~80%, and ~85% relative to wild-type, Irs1tm1Jos, and Irs3tm1Lhd mice, respectively
• in contrast, the interscapular brown fat pad appears unaffected with respect to color and size
• notably, injection of leptin adenovirus leads to a further reduction in white adipose tissue mass (reduced perigonadal fat pads); no significant body weight changes are observed
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• double homozygotes exhibit reduced adipocyte size of perigonadal fat pads relative to wild-type, Irs1tm1Jos and Irs3tm1Lhd mice
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• double homozygotes exhibit an increase in pancreatic beta-cell mass
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• both male and female double homozygotes display severe islet (beta-cell) hyperplasia, with a 4.3-fold increase relative wild-type and Irs3tm1Lhd mice, and a 1.9-fold increase relative to Irs1tm1Jos mice
• notably, the mass and distribution of non-beta-cells is similar between the various groups of mice
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| N |
• double mutant livers appear normal in color; no increased fat deposition is observed
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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 04/23/2024 MGI 6.23 |
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