Phenotypes Associated with This Genotype

Genotype
MGI:3582643

• Allelic Composition: Eif2ak3^tm1Dron/Eif2ak3^tm1Dron
• Genetic Background: involves: 129S6/SvEvTac * Swiss Webster

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

mortality/aging

postnatal lethality ( J:70005 )

• about half the expected number of homozygous mice were recovered at weaning

growth/size/body

decreased body weight ( J:70005 )

postnatal growth retardation ( J:70005 )

homeostasis/metabolism

steatorrhea ( J:70005 )

• resulted from pancreatic maldigestion

hyperglycemia ( J:70005 )

• seen after 4 weeks of age, primarily due to the failure of the endocrine pancreas to secrete adequate amounts of insulin

decreased circulating insulin level ( J:70005 )

digestive/alimentary system

abnormal exocrine pancreas morphology ( J:70005 )

• increased cell death in the exocrine pancreas

• the endoplasmic reticulum (ER) in the exocrine pancreas was segmented instead of organized into long, thin, densely packed cisterna and its lumen was distended with material of higher electron density than the contents of wildtype ER

steatorrhea ( J:70005 )

• resulted from pancreatic maldigestion

exocrine pancreatic insufficiency ( J:70005 )

• observed in most homozygotes by 6-8 weeks of age

endocrine/exocrine glands

abnormal exocrine pancreas morphology ( J:70005 )

• increased cell death in the exocrine pancreas

• the endoplasmic reticulum (ER) in the exocrine pancreas was segmented instead of organized into long, thin, densely packed cisterna and its lumen was distended with material of higher electron density than the contents of wildtype ER

abnormal pancreatic islet morphology ( J:70005 )

• observed occasional cells with striking, abundant, and dilated membrane-bounded cisterna filled with a dense content and these cells generally had fewer secretory granules

• with time, size of islets decreased

increased pancreatic alpha cell number ( J:70005 )

• with time, proportion of glucagon-positive cells increased and they were found to populate the core of the islet as well as its mantle

decreased pancreatic beta cell number ( J:70005 )

• with time, the mass of insulin-producing cells diminished

abnormal pancreas physiology ( J:70005 )

• increased levels of endoplasmic reticulum stress in the pancreas

exocrine pancreatic insufficiency ( J:70005 )

• observed in most homozygotes by 6-8 weeks of age

abnormal pancreatic beta cell physiology ( J:70005 )

• increased glucose-induced proinsulin biosynthesis in islets of Langerhans, however processing of proinsulin was normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Wolcott-Rallison syndrome		DOID:0090060	OMIM:226980	J:70005