Phenotypes Associated with This Genotype

Genotype
MGI:8250768

• Allelic Composition: Lama5^mpc205H/Lama5^mpc205H
• Genetic Background: B6(Cg)-Lama5^mpc205H

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

renal/urinary system

increased urine protein level ( J:344185 )

• proteinuria at 25 weeks, but not at 5 or 15 weeks, of age on a congenic C57BL/6J background, as assessed by the urinary protein-to-urinary creatinine ratio

• Background Sensitivity: significant proteinuria at 15 weeks of age on a congenic C3 background

podocyte foot process effacement ( J:344185 )

• complete foot process effacement with loss of any interdigital structure at 25 weeks, but not at 15 weeks, of age on a congenic C57BL/6J background

• Background Sensitivity: complete foot process effacement at 15 weeks of age on a congenic C3 background

abnormal renal glomerulus basement membrane morphology ( J:344185 )

• irregular glomerulus basement membrane (GBM) morphology with podocyte foot process invasion at 25 weeks, but not at 5 or 15 weeks, of age on a congenic C57BL/6J background

• proteomic analysis of the glomerular extracellular fraction shows altered matrix composition with reduced abundance of LAMA5, LAMC1 (laminin, gamma 1) and NTN4 (netrin 4) at both 15 and 25 weeks, lower abundance of AGRN (agrin) at 25 weeks, and increased abundance of vitronectin (VTN) at 25 weeks of age

increased renal glomerulus basement membrane thickness ( J:344185 )

• focal thickening of the GBM at 25 weeks, but not at 5 or 15 weeks, of age on a congenic C57BL/6J background

abnormal kidney physiology ( J:344185 )

• nephrotic syndrome phenotypes associated with hypercholesterolemia and hypoalbuminemia, but normal plasma creatinine levels and creatinine clearance rate (an indicator of glomerular filtration rate), at 25 weeks of age on a congenic C57BL/6J background

• Background Sensitivity: delayed disease progression with better kidney function on a congenic C57BL/6J background than on a mixed 62.5% C57BL/6J and 37.5% C3H background at 6 months of age

• Background Sensitivity: accelerated disease progression with proteinuria, hypoalbuminemia, hypercholesterolemia, and ultrastructural kidney changes at 15 weeks of age on a congenic C3 background

homeostasis/metabolism

increased blood urea nitrogen level ( J:344185 )

• small but significant increase in plasma urea level at 25 weeks, but not at 5 or 15 weeks, of age on a congenic C57BL/6J background

• Background Sensitivity: significant increase in plasma urea level at 15 weeks of age on a congenic C3 background

increased circulating cholesterol level ( J:344185 )

• significantly increased plasma total cholesterol levels at 25 weeks, but not at 5 or 15 weeks, of age on a congenic C57BL/6J background

• Background Sensitivity: significantly increased plasma total cholesterol levels at 15 weeks of age on a congenic C3 background

increased circulating HDL cholesterol level ( J:344185 )

• significantly increased plasma HDL levels at 25 weeks, but not at 5 or 15 weeks, of age on a congenic C57BL/6J background

• Background Sensitivity: significantly increased plasma HDL levels at 15 weeks of age on a congenic C3 background

increased circulating LDL cholesterol level ( J:344185 )

• significantly increased plasma LDL levels at 25 weeks, but not at 5 or 15 weeks, of age on a congenic C57BL/6J background

decreased circulating serum albumin level ( J:344185 )

• mild hypoalbuminemia at 15 weeks becoming more pronounced at 25 weeks of age on a congenic C57BL/6J background

• Background Sensitivity: significantly lower plasma albumin levels on a congenic C3 background than on a congenic C57BL/6J background at 15 weeks of age

increased urine protein level ( J:344185 )

• proteinuria at 25 weeks, but not at 5 or 15 weeks, of age on a congenic C57BL/6J background, as assessed by the urinary protein-to-urinary creatinine ratio

• Background Sensitivity: significant proteinuria at 15 weeks of age on a congenic C3 background

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial nephrotic syndrome		DOID:2590	OMIM:PS256300	J:344185