Phenotypes Associated with This Genotype

Genotype
MGI:5504390

• Allelic Composition: Met^tm1Sst/Met^tm1Sst; Tg(Pdx1-cre)89.1Dam/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:196854 )

♀ • islets from pregnant mutants do not exhibit an increase in insulin content as seen in pregnant wild-type females

decreased pancreatic beta cell mass ( J:196854 )

♀ • pregnant females show decreased beta cell mass at gestational day 19 compared to controls, at a time when maximal beta-cell mass expansion occurs during pregnancy

♀ • the decrease in beta-cell mass persists at postpartum day 4

♀ • however, islet number and beta-cell size are similar to wild-type at gestational day 19

abnormal pancreatic beta cell physiology ( J:196854 )

♀ • apoptosis in beta-cells of mutant pregnant females is premature and is increased at gestational day 15, however at gestational day 19 and postpartum day 4, beta cell apoptosis is increased similarly in wild-type and mutant pregnant females

♀ • mutant beta cells are more sensitive to the cytotoxic effects of a low dose of the synthetic hormone dexamethasone that does not induce cell death in wild-type islets

decreased pancreatic beta cell proliferation ( J:196854 )

♀ • pregnant females show a decrease in beta-cell proliferation at gestational day 15, when maximal beta-cell proliferation normally occurs during pregnancy

♀ • beta-cell proliferation is also decreased at postpartum day 4

♀ • however, beta-cell proliferation is similar to wild-type at gestational day 11 and 19

decreased insulin secretion ( J:196854 )

♀ • islets from pregnant mutants do not exhibit an increase in insulin content as seen in pregnant wild-type females

♀ • islets from mutant pregnant females do not exhibit an increase in glucose-stimulated insulin secretion at gestational day 19 that is seen in wild-type pregnant females

homeostasis/metabolism

decreased insulin secretion ( J:196854 )

♀ • islets from pregnant mutants do not exhibit an increase in insulin content as seen in pregnant wild-type females

♀ • islets from mutant pregnant females do not exhibit an increase in glucose-stimulated insulin secretion at gestational day 19 that is seen in wild-type pregnant females

increased circulating glucose level ( J:196854 )

♀ • blood glucose is higher in pregnant mutant females at gestational day 19 than in wild-type pregnant females

♀ • fasting blood glucose is increased in pregnant mutant females at gestational day 19 than in wild-type pregnant females

decreased circulating insulin level ( J:196854 )

♀ • plasma insulin levels are diminished in pregnant mutant females at gestational day 19 compared to wild-type pregnant females

impaired glucose tolerance ( J:196854 )

♀ • glucose tolerance is impaired more in pregnant mutant females than pregnant wild-type females at gestational day 15 and 19 and at postpartum day 4

♀ • pregnant mutant females respond similarly to insulin tolerance tests at gestational day 18 as wild-type females, indicating that enhanced impairment in glucose tolerance is not related to changes in insulin sensitivity

cellular

decreased pancreatic beta cell proliferation ( J:196854 )

♀ • pregnant females show a decrease in beta-cell proliferation at gestational day 15, when maximal beta-cell proliferation normally occurs during pregnancy

♀ • beta-cell proliferation is also decreased at postpartum day 4

♀ • however, beta-cell proliferation is similar to wild-type at gestational day 11 and 19

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
gestational diabetes		DOID:11714		J:196854