|
Allele Symbol Allele Name Allele ID |
Pdpk1tm1Maka targeted mutation 1, Masato Kasuga MGI:3628819 |
||||||||||||||||||||||||||||||||||||||||||||
| Summary |
10 genotypes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• insulin-induced inhibition of hepatic glucose production with a euglycemic clamp is attenuated even more than in single knockouts for either Stat3 or Pdk1
|
|
• glucose tolerance is impaired further compared to conditional single Pdk1-null mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice a tend towards increased in body weight compared with Pdpk1tm1Maka/Pdpk1tm1Maka Tg(CAG-cat-lacZ)11Miya Tg(Pomc1-cre)16Lowl mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• female mice exhibit a tended towards increased adiposity compared with wild-type mice
|
|
• mice exhibit increased food intake compared with wild-type mice and Pdpk1tm1Maka/Pdpk1tm1Maka Tg(CAG-cat-lacZ)11Miya Tg(Pomc1-cre)16Lowl mice
|
|
• at 16 weeks, mice are significantly heavier than Pdpk1tm1Maka/Pdpk1tm1Maka Tg(CAG-cat-lacZ)11Miya Tg(Pomc1-cre)16Lowl mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit increased apoptosis in the pituitary compared with wild-type mice
|
|
• mice exhibit a decrease in corticotrophs in the anterior pituitary due to apoptosis unlike in wild-type mice
• however, corticotroph development in the anterior pituitary at E18.5 is normal
|
|
• mice exhibit a decrease in melanotrophs in the intermediate pituitary due to apoptosis unlike in wild-type mice
• however, melanotrophs development in the intermediate pituitary at E18.5 is normal
|
|
• extremely thin
|
|
• Pomc1 neurons exhibit a blunted influx of calcium ions in response to leptin compared with similarly treated wild-type neurons
|
|
• following intraperitoneal leptin injection, mice exhibit a lesser decrease in body weight and food intake compared with similarly treated wild-type mice
|
|
• at 16 weeks in fed and fasted states
|
|
• especially visceral fat mass
|
|
• food intake is increased compared to in wild-type mice
|
|
• mice exhibit increased apoptosis in the pituitary compared with wild-type mice
|
|
• mice exhibit a decrease in corticotrophs in the anterior pituitary due to apoptosis unlike in wild-type mice
• however, corticotroph development in the anterior pituitary at E18.5 is normal
|
|
• mice exhibit a decrease in melanotrophs in the intermediate pituitary due to apoptosis unlike in wild-type mice
• however, melanotrophs development in the intermediate pituitary at E18.5 is normal
|
|
• extremely thin
|
|
• mice exhibit increased apoptosis in the pituitary compared with wild-type mice
|
|
• mice exhibit a decrease in corticotrophs in the anterior pituitary due to apoptosis unlike in wild-type mice
• however, corticotroph development in the anterior pituitary at E18.5 is normal
|
|
• mice exhibit a decrease in melanotrophs in the intermediate pituitary due to apoptosis unlike in wild-type mice
• however, melanotrophs development in the intermediate pituitary at E18.5 is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• although some primordial follicles are activated by P23, not all of them are activated as seen in single conditional homozygous Tsc1 mutants, indicating partial reversal of the overactivation of primordial follicles
|
|
|
• although some primordial follicles are activated by P23, not all of them are activated as seen in single conditional homozygous Tsc1 mutants, indicating partial reversal of the overactivation of primordial follicles
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• females are sterile, however follicular development and oocyte maturation are normal
• fertilization is also normal in mutant females, with numbers of two-cell embryos from pregnant females comparable with those from controls
|
|
• 92.5% of two-cell embryos from mutant females mated with wild-type males arrest at the two-cell stage when cultured in vitro compared to 4.2% of wild-type control embryos; heterozygous embryos do not express PDPK1 protein, indicating that this protein is not yet synthesized from the paternal allele in these embryos
• two-cell embryos resulting from mutant female mating to wild-type males exhibit suppression of embryonic genome activation and defective G2-to-M transition of the second mitotic cell cycle
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• fertility of double mutant females is completely restored from 10-30 weeks of age when mated with wild-type males compared to single conditional homozygous Pdpk1 mutants
• embryos derived from double mutant females mated with wild-type males show normal perimplantation development, indicating rescue of the two-cell arrest and the suppressed embryonic genome activation seen in embryos from single conditional homozygous Pdpk1 mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all male knockouts die between 12 and 24 weeks of age from uncontrolled diabetes
|
|
• after 8 weeks of age, mutant body weights increase at a lower rate compared to control
|
|
• mutants exhibit hyperglycemia with blood glucose levels greater than 500 mg/dl by 12-16 weeks of age
|
|
• at 12 weeks of age, plasma insulin in the fed state is lower in mutants; by 20 weeks of age, it is close to the lower detection limit
|
|
• beta cells proliferate much less in islets of null mice; proliferation is ~50% lower at 4 weeks and ~75% lower at 8 weeks
|
|
• at 4 weeks of age, size of islets is smaller than in controls; islet density is lower than in controls and is only ~40% that of controls at 16 weeks
|
|
• insulin content of the pancreas in null mice is lower than in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• double mutants have improved blood glucose levels compared to Pdk1-deficient mice; glucose levels of 200-300 mg/dl are maintained in double mutants at 20-24 weeks
|
|
• plasma insulin level is significantly higher in double mutants compared to Pdk1-deficient mice
|
|
• Foxo-haploinsufficiency results in a significant increase in beta cell number in double mutants
|
|
• insulin content of the pancreas in double mutant mice is 6-fold higher than in Pdk1-deficient mice; number of proliferating beta cells is much greater in double mutants compared to Pdk1-null mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• insulin-induced inhibition of hepatic glucose production with a euglycemic clamp is attenuated
|
|
• mice display an exaggerated increase in glucose concentration during a glucose-tolerance test
|
|
• insulin levels are high compared to controls and other mutant lines
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
||
|
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support. |
last database update 04/23/2024 MGI 6.23 |
|
|
|
||
Analysis Tools