Mouse Genome Informatics
ht
    Ins2Akita/Ins2+
C57BL/6-Ins2Akita
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• 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
• 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)
• 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)
• insulin levels are decreased in the blood and pancreas

endocrine/exocrine glands
• 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
• partial degranulation
• 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 (J:108948)
• 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
• seen in all diabetic males but only 5 of 20 diabetic females
• develops soon after weaning and is more severe in males

behavior/neurological
• 7-8 week old males consume 7 fold more water as compared to controls (33.28 ml/day v. 4.68 ml/day) (J:125256)
• develops soon after weaning and is more severe in males
• 7-8 week old males consume 2 fold more food as compared to controls (8.16 g/day v. 4.48 g/day) (J:125256)
• 7-8 week old males exhibit greater anxiety behavior in elevated plus maze (J:125256)
• total number and total time of entries in the open arms is significantly decreased as compared to controls (J:125256)
• 7-8 week old males exhibit increased immobility time as measured in open field test (J:125256)
• 7-8 week old males exhibit decreased locomotor activity as measured in open field test (J:125256)
• number of total entries in elevated plus maze is decreased in 7-8 week old males as compared to controls (J:125256)

growth/size
• 7-8 week old males exhibit decreased weight as compared to controls (24g v. 26g) (J:125256)
• 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
• mutants have almost no subcutaneous fat

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

reproductive system
• 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 (J:108948)

skeleton
• diabetic mice display kyphosis but to a lesser extent than double mutant mice
• mutants have significantly reduced bone density compared to wild-type or Bdkrb2-deficient mice

integument
• mutants have almost no subcutaneous fat

Mouse Models of Human Disease
OMIM IDRef(s)
Maturity-Onset Diabetes of the Young; MODY 606391 J:40063