Phenotypes Associated with This Genotype

Genotype
MGI:3842791

• Allelic Composition: Tg(Ckm-IGF1R*K1003R)1Dlr/0
• Genetic Background: FVB/N-Tg(Ckm-IGF1R*K1003R)1Dlr

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

homeostasis/metabolism

increased circulating creatinine level ( J:210518 )

♂ • mice subjected to uninephrectomy exhibit increased serum creatinine compared to wild-type mice

increased circulating cholesterol level ( J:210518 )

♂ • serum cholesterol is increased; diet has no effect on cholesterol levels

increased circulating free fatty acids level ( J:71205 )

• 2-fold at 3 to 4 weeks of age

increased circulating triglyceride level ( J:71205 )

• 2-fold at 3 to 4 weeks of age

abnormal glucose homeostasis ( J:71205 )

• total body glucose disposal, glycolysis, and glycogen synthesis are reduced compared to in wild-type mice

increased circulating glucose level ( J:71205 )

hyperglycemia ( J:210518 )

♂ • seen in mice fed a regular chow diet

♂ • mice subjected to uninephrectomy remain hyperglycemic

increased circulating insulin level ( J:71205 )

• at 2 weeks of age

impaired glucose tolerance ( J:71205 )

• at 7 to 12 weeks

abnormal glycogen homeostasis ( J:71205 )

• glycogen synthesis is reduced compared to in wild-type mice

insulin resistance ( J:71205 )

increased liver triglyceride level ( J:71205 )

albuminuria ( J:210518 )

♂ • 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

abnormal response/metabolism to endogenous compounds ( J:71205 )

• following stimulation with IGF-I, muscle fails to exhibit an increase in glucose uptake unlike in similarly treated wild-type muscle

muscle

decreased muscle cell glucose uptake ( J:71205 )

• 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

pancreatic islet hyperplasia ( J:71205 )

cellular

decreased cellular glucose uptake ( J:71205 )

• glucose transport activity in skeletal muscle and brown adipose tissue is reduced 50% compared to in wild-type cells

decreased muscle cell glucose uptake ( J:71205 )

• 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

growth/size/body

decreased body weight ( J:71205 )

• 20% from birth to 4 weeks of age and 10% from 4 weeks of age through adulthood

postnatal growth retardation ( J:71205 )

• 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

slow postnatal weight gain ( J:210518 )

♂ • mice subjected to uninephrectomy remain hyperglycemic but gain less body weight than wild-type mice

increased kidney weight ( J:210518 )

♂ • 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

liver/biliary system

increased liver triglyceride level ( J:71205 )

cardiovascular system

increased systemic arterial blood pressure ( J:210518 )

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

renal/urinary system

increased kidney weight ( J:210518 )

♂ • 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

albuminuria ( J:210518 )

♂ • 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

podocyte foot process effacement ( J:210518 )

♂ • mice fed a high-fat diet exhibit foot process effacement

♂ • mice subjected to uninephrectomy exhibit accelerated foot process effacement

decreased podocyte number ( J:210518 )

♂ • mice fed a high-fat diet exhibit a decrease in podocyte number

♂ • mice subjected to uninephrectomy exhibit an accelerated decrease in podocyte number

increased renal glomerulus basement membrane thickness ( J:210518 )

♂ • increase in glomerular basement membrane thickening, regardless of diet

♂ • mutants subjected to uninephrectomy exhibit accelerated basement membrane thickening

abnormal renal glomerulus morphology ( J:210518 )

♂ • 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

abnormal glomerular mesangium morphology ( J:210518 )

♂ • increase in mesangial expansion, regardless of diet

♂ • mutants subjected to uninephrectomy exhibit accelerated mesangial expansion

increased renal glomerular filtration rate ( J:210518 )

♂ • glomerular hyperfiltration, as seen with an increase in glomerular filtration rate at 10 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:71205 , J:210518