Phenotypes Associated with This Genotype

Genotype
MGI:3583904

• Allelic Composition: Ins2^Akita/Ins2⁺
• Genetic Background: C57BL/6-Ins2^Akita

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

mortality/aging

premature death ( J:40063 , J:108948 )

• mice have much shorter lifespan than wild-type; 909 days (wt) vs 373 days (mutant) (J:108948)

♂ • 50% survival time in males is reduced to 305 days but survival time is not reduced for females through 370 days of age (J:40063)

homeostasis/metabolism

decreased insulin secretion ( J:40063 , J:47883 )

• hyposecretion of insulin is seen; however, islet area is not reduced (J:40063)

• the pancreatic ratio of insulin to glucagon is decreased to 0.42 and 0.54 at birth and 14 days of age, respectively compared to 1.17 and 1.11 in wild-type mice (J:47883)

hyperglycemia ( J:40063 , J:125256 )

• develops soon after weaning and is more severe in males (J:40063)

♂ • blood glucose in fed 7-8 week old males measures 544+/-11 mg/dl (J:125256)

decreased circulating insulin level ( J:40063 )

• insulin levels are decreased in the blood and pancreas

impaired glucose tolerance ( J:40063 )

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:47883 )

• density of beta cells is decreased at 14 days of age

• beta cells have increased amounts of endoplasmic reticulum and Golgi complexes, more and enlarged mitochondria, and partial degranulation

degranulated pancreatic beta cells ( J:47883 )

• partial degranulation

abnormal Leydig cell morphology ( J:108948 )

♂ • mutant males display some pigmented vacuoles in Leydig cells in the testes, but to a lesser extent than in double mutant males at 12 months of age

decreased insulin secretion ( J:40063 , J:47883 )

• hyposecretion of insulin is seen; however, islet area is not reduced (J:40063)

• the pancreatic ratio of insulin to glucagon is decreased to 0.42 and 0.54 at birth and 14 days of age, respectively compared to 1.17 and 1.11 in wild-type mice (J:47883)

renal/urinary system

hydronephrosis ( J:40063 )

• seen in all diabetic males but only 5 of 20 diabetic females

polyuria ( J:40063 )

• develops soon after weaning and is more severe in males

behavior/neurological

increased fluid intake ( J:125256 )

♂ • 7-8 week old males consume 7 fold more water as compared to controls (33.28 ml/day v. 4.68 ml/day)

polydipsia ( J:40063 )

• develops soon after weaning and is more severe in males

polyphagia ( J:125256 )

♂ • 7-8 week old males consume 2 fold more food as compared to controls (8.16 g/day v. 4.48 g/day)

increased anxiety-related response ( J:125256 )

♂ • 7-8 week old males exhibit greater anxiety behavior in elevated plus maze

♂ • total number and total time of entries in the open arms is significantly decreased as compared to controls

akinesia ( J:125256 )

♂ • 7-8 week old males exhibit increased immobility time as measured in open field test

decreased locomotor activity ( J:125256 )

♂ • 7-8 week old males exhibit decreased locomotor activity as measured in open field test

♂ • number of total entries in elevated plus maze is decreased in 7-8 week old males as compared to controls

growth/size/body

decreased body weight ( J:125256 )

♂ • 7-8 week old males exhibit decreased weight as compared to controls (24g v. 26g)

postnatal growth retardation ( J:40063 )

• weight gain is normal through 18 weeks of age but then no further weight gain is seen and by 30 weeks weight loss is observed

adipose tissue

decreased subcutaneous adipose tissue amount ( J:108948 )

• mutants have almost no subcutaneous fat

cellular

abnormal mitochondrial morphology ( J:108948 )

• mutant mice show greater mitochondrial damage than wild-type or Bdkrb2-deficient mice at 12 months of age

reproductive system

abnormal Leydig cell morphology ( J:108948 )

♂ • mutant males display some pigmented vacuoles in Leydig cells in the testes, but to a lesser extent than in double mutant males at 12 months of age

skeleton

kyphosis ( J:108948 )

• diabetic mice display kyphosis but to a lesser extent than double mutant mice

decreased bone mineral density ( J:108948 )

• mutants have significantly reduced bone density compared to wild-type or Bdkrb2-deficient mice

integument

decreased subcutaneous adipose tissue amount ( J:108948 )

• mutants have almost no subcutaneous fat

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maturity-onset diabetes of the young		DOID:0050524	OMIM:606391	J:40063