Mouse Genome Informatics
tg
    Tg(Ckm-IGF1R*K1003R)1Dlr/0
FVB/N-Tg(Ckm-IGF1R*K1003R)1Dlr
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• mice subjected to uninephrectomy exhibit increased serum creatinine compared to wild-type mice
• serum cholesterol is increased; diet has no effect on cholesterol levels
• 2-fold at 3 to 4 weeks of age
• 2-fold at 3 to 4 weeks of age
• total body glucose disposal, glycolysis, and glycogen synthesis are reduced compared to in wild-type mice
• seen in mice fed a regular chow diet
• mice subjected to uninephrectomy remain hyperglycemic
• at 7 to 12 weeks
• glycogen synthesis is reduced compared to in wild-type mice
• mice exhibit albuminuria at 30 weeks of age
• after 24 weeks of high-fat diet feeding, mutants exhibit a significant increase in albuminuria than low-fat diet fed mutants
• mutants subjected to uninephrectomy exhibit accelerated albuminuria
• following stimulation with IGF-I, muscle fails to exhibit an increase in glucose uptake unlike in similarly treated wild-type muscle

muscle
• insulin stimulated glucose uptake is 1.5-fold compared to 5-fold in wild-type mice
• following stimulation with IGF-I, muscle fails to exhibit an increase in glucose uptake unlike in similarly treated wild-type muscle

endocrine/exocrine glands

cellular
• insulin stimulated glucose uptake is 1.5-fold compared to 5-fold in wild-type mice
• following stimulation with IGF-I, muscle fails to exhibit an increase in glucose uptake unlike in similarly treated wild-type muscle
• glucose transport activity in skeletal muscle and brown adipose tissue is reduced 50% compared to in wild-type cells

growth/size/body
• 20% from birth to 4 weeks of age and 10% from 4 weeks of age through adulthood
• mice exhibit modest growth retardation from birth to 4 weeks of age and a smaller reduction in growth from 4 weeks of age through adulthood compared to in wild-type mice
• mice subjected to uninephrectomy remain hyperglycemic but gain less body weight than wild-type mice

liver/biliary system

cardiovascular system
• mice subjected to uninephrectomy exhibit elevated systolic and diastolic blood pressure compared to wild-type mice

renal/urinary system
• mice exhibit albuminuria at 30 weeks of age
• after 24 weeks of high-fat diet feeding, mutants exhibit a significant increase in albuminuria than low-fat diet fed mutants
• mutants subjected to uninephrectomy exhibit accelerated albuminuria
• mice fed a high-fat diet exhibit foot process effacement
• mice subjected to uninephrectomy exhibit accelerated foot process effacement
• mice fed a high-fat diet exhibit a decrease in podocyte number
• mice subjected to uninephrectomy exhibit an accelerated decrease in podocyte number
• increase in glomerular basement membrane thickening, regardless of diet
• mutants subjected to uninephrectomy exhibit accelerated basement membrane thickening
• mice exhibit glomerular injury at baseline
• increase in glomerular volume, regardless of diet
• mice fed a high-fat diet for 24 weeks exhibit acceleration of glomerulopathy compared to wild-type mice, showing an increase in mesangial expansion, foot process effacement and glomerular basement membrane thickening, and a decrease in podocyte number
• mutants subjected to uninephrectomy exhibit accelerated glomerular injury compared to similarly subjected wild-type mice or to high-fat diet fed mutants, showing increased albuminuria, kidney weight, mesangial expansion, foot process effacement, glomerular volume and glomerular basement membrane thickening and a decrease in podocyte number
• increase in mesangial expansion, regardless of diet
• mutants subjected to uninephrectomy exhibit accelerated mesangial expansion
• larger kidney weight at 30 weeks of age; diet has no effect on kidney weight
• mutants subjected to uninephrectomy exhibit accelerated increase in kidney weight
• glomerular hyperfiltration, as seen with an increase in glomerular filtration rate at 10 weeks of age

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:71205 , J:210518