Phenotypes associated with this allele

• Allele Symbol: Lama5^mpc205H
• Allele Name: muta-ped-c3pde 205, Harwell
• Allele ID: MGI:5792034
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lama5^mpc205H/Lama5^mpc205H	B6(Cg)-Lama5^mpc205H	MGI:8250768
hm2	Lama5^mpc205H/Lama5^mpc205H	C3.B6(C)-Lama5^mpc205H	MGI:8250788
hm3	Lama5^mpc205H/Lama5^mpc205H	involves: BALB/c * C3H/HeH * C57BL/6J	MGI:5792353
ht4	Lama5^mpc205H/Lama5^+	involves: BALB/c * C3H/HeH * C57BL/6J	MGI:8250771
ht5	Lama5^mpc205H/Lama5^tm1b(KOMP)Wtsi	involves: BALB/c * C3H/HeH * C57BL/6J * C57BL/6N	MGI:8250774

Genotype
MGI:8250768

hm1

• 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

Genotype
MGI:8250788

hm2

• Allelic Composition: Lama5^mpc205H/Lama5^mpc205H
• Genetic Background: C3.B6(C)-Lama5^mpc205H

renal/urinary system

increased urine protein level ( J:344185 )

• significant proteinuria at 15 weeks of age on a congenic C3 background, as assessed by the urinary protein-to-urinary creatinine ratio

• Background Sensitivity: proteinuria at 25 weeks, but not at 5 or 15 weeks, of age on a congenic C57BL/6J background

podocyte foot process effacement ( J:344185 )

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

• Background Sensitivity: 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

renal glomerulus fibrosis ( J:344185 )

• fibrotic glomeruli at 15 weeks of age on a congenic C3 background

dilated renal tubule ( J:344185 )

• dilated tubules with protein casts at 15 weeks of age on a congenic C3 background

renal cast ( J:344185 )

• dilated tubules with protein casts at 15 weeks of age on a congenic C3 background

abnormal kidney physiology ( J:344185 )

• accelerated nephrotic syndrome progression with proteinuria, hypoalbuminemia, hypercholesterolemia, and ultrastructural kidney changes at 15 weeks of age on a congenic C3 background

• Background Sensitivity: delayed disease progression on a congenic C57BL/6J background, with only mild hypoalbuminemia at 15 weeks, and proteinuria and foot process effacement only detectable at 25 weeks of age

homeostasis/metabolism

increased circulating creatinine level ( J:344185 )

• increased plasma creatinine levels at 15 weeks of age on a congenic C3 background

• Background Sensitivity: normal plasma creatinine levels on a congenic C57BL/6J background up to 25 weeks of age

increased blood urea nitrogen level ( J:344185 )

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

• Background Sensitivity: 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

increased circulating cholesterol level ( J:344185 )

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

• Background Sensitivity: significant elevation of plasma total cholesterol levels at 25 weeks, but not at 15 weeks, of age on a congenic C57BL/6J background

increased circulating HDL cholesterol level ( J:344185 )

• increased plasma HDL levels at 15 weeks of age on a congenic C3 background

• Background Sensitivity: significant elevation of plasma HDL levels at 25 weeks, but not at 15 weeks, of age on a congenic C57BL/6J background

hyperlipidemia ( J:344185 )

• increased plasma total cholesterol and HDL levels at 15 weeks of age on a congenic C3 background

• Background Sensitivity: significant hyperlipidemia at 25 weeks, but not at 15 weeks, of age on a congenic C57BL/6J background

decreased circulating serum albumin level ( J:344185 )

• significant decrease in plasma albumin levels at 15 weeks of age on a congenic C3 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 )

• significant proteinuria at 15 weeks of age on a congenic C3 background, as assessed by the urinary protein-to-urinary creatinine ratio

• Background Sensitivity: proteinuria at 25 weeks, but not at 5 or 15 weeks, of age on a congenic C57BL/6J background

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

Genotype
MGI:5792353

hm3

• Allelic Composition: Lama5^mpc205H/Lama5^mpc205H
• Genetic Background: involves: BALB/c * C3H/HeH * C57BL/6J

renal/urinary system

increased urine protein level ( J:344185 )

• Background Sensitivity: proteinuria at 7 weeks of age in mice backcrossed 1 generation to the C3H background

• Background Sensitivity: proteinuria at 25 weeks of age on a congenic C57BL/6J background

abnormal renal glomerular capsule morphology ( J:344185 )

• fibrosis of the Bowman capsule at 6 months of age

dilated renal tubule ( J:344185 )

• dilated tubules with protein casts at 6 months of age

renal cast ( J:344185 )

• dilated tubules with protein casts at 6 months of age

kidney failure ( J:234901 , J:344185 )

• progressive nephrotic syndrome leading to end-stage renal failure between 7 and 10 months of age (J:234901)

• health of affected mice reaches welfare limits around 248 +/- 13.7 days of age due to chronic kidney disease (J:344185)

• Background Sensitivity: delayed disease progression with improved kidney function on a congenic C57BL/6J background relative to a mixed 62.5% C57BL/6J and 37.5% C3H background at 6 months of age (J:344185)

homeostasis/metabolism

increased circulating creatinine level ( J:234901 , J:344185 )

• increased plasma creatinine levels from 6 months of age (J:234901)

• Background Sensitivity: increased plasma creatinine levels at 15 weeks of age in mice backcrossed 1 generation to the C3H background (J:344185)

increased blood urea nitrogen level ( J:234901 , J:344185 )

• increased plasma urea levels from 6 months of age (J:234901)

• Background Sensitivity: increased plasma urea levels at 15 weeks of age in mice backcrossed 1 generation to the C3H background (J:344185)

decreased circulating serum albumin level ( J:234901 , J:344185 )

• decreased plasma albumin levels from 6 months of age (J:234901)

• plasma albumin levels are 2 SDs below littermate range at 6 months of age (J:344185)

• Background Sensitivity: hypoalbuminemia as early as 12 weeks of age in mice backcrossed 1 generation to the C3H background (J:344185)

increased urine protein level ( J:344185 )

• Background Sensitivity: proteinuria at 7 weeks of age in mice backcrossed 1 generation to the C3H background

• Background Sensitivity: proteinuria at 25 weeks of age on a congenic C57BL/6J background

Genotype
MGI:8250771

ht4

• Allelic Composition: Lama5^mpc205H/Lama5⁺
• Genetic Background: involves: BALB/c * C3H/HeH * C57BL/6J

renal/urinary system

renal/urinary system phenotype ( J:344185 )

N • normal kidney function at 22 weeks of age, as determined by plasma creatinine, urea and albumin levels

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:344185 )

N • normal levels of plasma creatinine, urea and albumin levels at 6 months of age

Genotype
MGI:8250774

ht5

• Allelic Composition: Lama5^mpc205H/Lama5^{tm1b(KOMP)Wtsi}
• Genetic Background: involves: BALB/c * C3H/HeH * C57BL/6J * C57BL/6N

homeostasis/metabolism

increased circulating creatinine level ( J:344185 )

• increased plasma creatinine levels at 22 weeks of age

increased blood urea nitrogen level ( J:344185 )

• increased plasma urea levels at 22 weeks of age

decreased circulating serum albumin level ( J:344185 )

• decreased plasma albumin levels at 22 weeks of age