Phenotypes Associated with This Genotype

Genotype
MGI:5789257

• Allelic Composition: Madd^tm1Bpra/Madd^tm1Bpra; Tg(Ins2-cre/ERT)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 pancreas morphology ( J:225256 )

• insulin content is increased in the pancreas of tamoxifen treated mice

abnormal pancreatic islet morphology ( J:225256 )

• total insulin content is higher in islets of tamoxifen treated mice than in controls

• islet cells from tamoxifen treated mice exhibit denser insulin granules in the beta-cells

• however, pancreatic islets exhibit normal morphology

abnormal pancreatic beta cell morphology ( J:225256 )

• beta cells from tamoxifen treated mice exhibit an increased accumulation of insulin

abnormal pancreatic beta cell physiology ( J:225256 )

• tamoxifen treated mice exhibit defective beta-cell function

decreased insulin secretion ( J:225256 )

• tamoxifen treated mice exhibit delayed glucose-stimulated insulin release

• islets from tamoxifen treated mice fail to show a timely increase in insulin secretion in response to glucose challenge or potassium chloride treatment

• however, tamoxifen treated mice exhibit normal insulin sensitivity and do not exhibit peripheral insulin resistance

homeostasis/metabolism

decreased insulin secretion ( J:225256 )

• tamoxifen treated mice exhibit delayed glucose-stimulated insulin release

• islets from tamoxifen treated mice fail to show a timely increase in insulin secretion in response to glucose challenge or potassium chloride treatment

• however, tamoxifen treated mice exhibit normal insulin sensitivity and do not exhibit peripheral insulin resistance

increased fasting circulating glucose level ( J:225256 )

• fasting plasma glucose levels are elevated in tamoxifen treated mice

hyperglycemia ( J:225256 )

• mice develop hyperglycemia by day 6 of tamoxifen treatment that reaches peak levels by day 10

decreased circulating insulin level ( J:225256 )

• fasting blood insulin levels are reduced in tamoxifen treated mice

• however, nonfasting blood insulin levels are normal in tamoxifen treated mice

• tamoxifen treated mice exhibit delayed and lower circulating insulin levels in response to a glucose challenge

impaired glucose tolerance ( J:225256 )

• blood glucose levels of tamoxifen treated mice are greatly increased during the intraperitoneal glucose tolerance test, indicating delayed blood glucose clearance

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:225256