Mouse Genome Informatics
tg
    Tg(Ins2-CALM1)26Ove/0
FVB-Tg(Ins2-CALM1)26Ove
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
cellular
• swollen mitochondria and broken mitochondrial double membranes are observed
• hearts have increased mitochondrial mass, as well as greater area and number
• respiratory control ratio (RCR) and state 3 respiration are significantly impaired in mitochondria

cardiovascular system
• hearts have many focal areas of damage with swollen mitochondria, mottled matrix and broken mitochondrial double membranes
• progressive increase in renal vascular resistance beginning at 3 months of age
• diastolic blood pressure is elevated in conscious mutants at 3 months of age when measured using a tail-cuff monitor
• by 8 months of age, both diastolic and systolic blood pressure is increased in conscious mutants
• under anesthesia, when measured by intravascular connulation, mutants exhibit a similar blood pressure to anesthetized controls, however this is reduced compared to conscious mutants

homeostasis/metabolism
• blood glucose levels are more than 2-fold higher than normal by 20 days after birth and continue to rise until at least 60 days of age (J:94602)
• some mutants develop hypoalbuminemia due to excessive loss of albumin
• albumin excretion rate increases progressively with age and exceeds 15,000 ug/24 hr at 9 months of age

adipose tissue
• loss of fat tissue by 5 months of age

growth/size
N
• mutants exhibit normal weight gain and body weight (J:94602)

liver/biliary system

renal/urinary system
• progressive increase in renal vascular resistance beginning at 3 months of age
• albumin excretion rate increases progressively with age and exceeds 15,000 ug/24 hr at 9 months of age
• kidney shows dilation of the ducts, atrophy of tubular cells, protein casts in the duct lumen, and prominent infiltration of mononuclear cells
• glomeruli exhibit a thickened and irregular basement membrane
• expanded mesangium showing enlarged mesangial fraction and mesangial volume, with the greatest rate increase during 2.5-6 months of age
• diffuse and nodular expansion of mesangial matrix in mutants over 2 months of age
• diffuse and nodular glomerulosclerotic lesions
• nodules are acellular and are similar to Kimmelsteil-Wilson lesions in size
• glomerular volume is enlarged, with the greatest rate increase during 2.5-6 months of age
• seen in many mutants over 5 months of age
• 2-fold increase in kidney weight between 2 and 5 months of age
• expansion of kidney tubules; average cortical tubule cross-sectional area (minus the lumen) is 34% greater in 9 month old mutants than controls
• significant fibrosis in the kidney by 5 months of age
• tubulointerstitial fibrosis
• many mutants over 5 months of age exhibit bladder stasis
• distended bladders are seen in many mutants over 5 months of age
• glomerular filtration rate increases significantly from 2 to 3 months of age but then decreases significantly from 5 to 9 months of age
• decline in glomerular filtration rate coincides with an increase in renal vascular resistance
• by 2 months of age

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:94602