Phenotypes Associated with This Genotype

Genotype
MGI:5576784

• Allelic Composition: Clock^m1Jt/Clock^m1Jt
• Genetic Background: involves: C57BL/6J

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

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:162641 )

• total islet area is reduced by around 20%

• trend toward decreased total pancreatic insulin content

small pancreatic islets ( J:162641 )

abnormal pancreas physiology ( J:162641 )

• islets lack a circadian rhythm, even after forskolin stimulation

• 23% decrease in proliferation of islets

• decrease in levels of expression and/or phase shifts of RNA oscillation of genes involved in insulin signaling, glucose sensing, and islet growth and development

increased pancreatic islet cell apoptosis ( J:162641 )

• trend toward increased islet apoptosis

decreased insulin secretion ( J:162641 )

• islets from 8 month old mutants show an approximate 50% reduction in glucose-stimulated insulin secretion and fail to respond to KCl, indicating a defect in insulin exocytosis

• islets display diminished insulin secretory responses to the cyclase activators forskolin and exendin 4, and 8-bromo-cAMP

• islets from young mice show impaired glucose-stimulated insulin secretion

homeostasis/metabolism

decreased insulin secretion ( J:162641 )

• islets from 8 month old mutants show an approximate 50% reduction in glucose-stimulated insulin secretion and fail to respond to KCl, indicating a defect in insulin exocytosis

• islets display diminished insulin secretory responses to the cyclase activators forskolin and exendin 4, and 8-bromo-cAMP

• islets from young mice show impaired glucose-stimulated insulin secretion

hyperglycemia ( J:162641 )

• glucose levels are elevated across the entire light/dark cycle in 4 month old mutants without a rise in insulin levels during the beginning of the feeding period as is seen in wild-type mice

• mutants show elevated fasting glucose levels at both Zeitgeber time 2 and Zeitgeber time 14

• however, fasting and fed glucose levels in 3 month old mice are normal

impaired glucose tolerance ( J:162641 )

• glucose tolerance tests show a 50% reduction in insulin release that corresponds with elevated glucose levels, particularly at the beginning of the dark period

• however, mice show normal insulin tolerance

increased insulin sensitivity ( J:162641 )

• 3 month old mice have enhanced insulin sensitivity

insulin resistance ( J:162641 )

• gradual onset of insulin resistance

cellular

increased pancreatic islet cell apoptosis ( J:162641 )

• trend toward increased islet apoptosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
diabetes mellitus		DOID:9351		J:162641