Phenotypes Associated with This Genotype

Genotype
MGI:7622052

• Allelic Composition: Lepr^db/Lepr^db
• Genetic Background: BKS.Cg-Dock7^m +/+ Lepr^db

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

growth/size/body

increased body weight ( J:346348 )

• mice show an increase in body weight

• injection with a CCL4 (MIP-1beta) mAb controls the increase in body weight such that no difference in weight is seen

enlarged kidney ( J:346348 )

• increase in kidney-to-body weight ratio indicating renal hypertrophy

• treatment with MIP-1beta mAb reduces renal hypertrophy

homeostasis/metabolism

increased circulating creatinine level ( J:346348 )

• increase in creatinine levels

• treatment with MIP-1beta mAb reduces creatinine levels

increased blood urea nitrogen level ( J:346348 )

• increase in BUN levels

• treatment with MIP-1beta mAb reduces BUN levels

hyperglycemia ( J:346348 )

• increase in blood sugar levels

• injection with MIP-1beta mAb moderately controls the hyperglycemia

increased circulating insulin level ( J:346348 )

• higher levels of serum insulin

• treatment with MIP-1beta mAb shows a time-dependent reduction in serum insulin levels, with significant difference after 3 weeks of mAb injection

increased circulating cholesterol level ( J:346348 )

• serum cholesterol levels are increased

• treatment with MIP-1beta mAb has no effect on serum cholesterol levels

increased circulating triglyceride level ( J:346348 )

• serum triglyceride levels are increased

• injection with MIP-1beta mAb reduces triglyceride levels

renal/urinary system

enlarged kidney ( J:346348 )

• increase in kidney-to-body weight ratio indicating renal hypertrophy

• treatment with MIP-1beta mAb reduces renal hypertrophy

kidney inflammation ( J:346348 )

• inflammatory protein expression levels in the kidneys are elevated

• treatment with MIP-1beta mAb reduces CCL4 (MIP-1beta), TNF-alpha, and IL-6 expression levels in the kidneys

increased glomerular capsule space ( J:346348 )

abnormal podocyte morphology ( J:346348 )

• podocyte injury

• treatment with MIP-1beta mAb reduces podocyte injury

abnormal renal glomerulus morphology ( J:346348 )

• kidneys show advanced vacuole formation and glomerular hypertrophy as early as 8 weeks of age, indicating glomerular damage

• by 12 weeks of age, significant structural changes are seen in the glomeruli, along with larger Bowmans spaces, lower glomerular cellular contents, and increased tubular lumens

• treatment with MIP-1beta mAb prevents renal damage and normalizes glomerular hypertrophy

abnormal glomerular mesangium morphology ( J:346348 )

• expanded mesangial regions

• treatment with MIP-1beta mAb attenuates the expansion of the mesangial regions

expanded mesangial matrix ( J:346348 )

• accumulation of extracellular matrix

• treatment with MIP-1beta mAb attenuates the accumulation of extracellular matrix

glomerulosclerosis ( J:346348 )

• mice develop glomerulosclerosis

• treatment with MIP-1beta mAb reduces renal glomerulosclerosis

renal glomerulus hypertrophy ( J:346348 )

• mice show glomerular hypertrophy as early as 8 weeks of age

• treatment with MIP-1beta mAb normalizes glomerular hypertrophy

renal fibrosis ( J:346348 )

• mice show enhanced collagen-positive areas in kidneys, indicating kidney fibrosis

• treatment with MIP-1beta mAb reduces kidney fibrosis

immune system

kidney inflammation ( J:346348 )

• inflammatory protein expression levels in the kidneys are elevated

• treatment with MIP-1beta mAb reduces CCL4 (MIP-1beta), TNF-alpha, and IL-6 expression levels in the kidneys

behavior/neurological

polydipsia ( J:346348 )

• mice exhibit polydipsia

• treatment with MIP-1beta mAb reduces polydipsia

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:346348