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Phenotypes Associated with This Genotype
Genotype
MGI:5432351
Allelic
Composition
Vhltm1Jae/Vhltm1Jae
Tg(NPHS2-cre)295Lbh/?
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(NPHS2-cre)295Lbh mutation (3 available)
Vhltm1Jae mutation (2 available); any Vhl mutation (17 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• premature death beginning at ~6 months of age in mice with the highest levels of albuminuria (>1000 ug/ml)
• however, nonproteinuric mice survive to >1 year of age without overt health problems

renal/urinary system
N
• at P5, all mice exhibit normal comma and S-shaped nephric figures as well as normal capillary loop stage and maturing stage glomeruli relative to wild-type controls
• no changes in peritubular microvessels or larger arterioles and veins are observed
• dilated glomerular capillary lumen noted in mice with severe albuminuria as early as 4 weeks of age
• mesangial hypercellularity noted in mice with severe albuminuria at 4 weeks of age
• at 4 weeks of age, mice exhibit varying levels of albuminuria ranging from no detectable albumin to >1000 ug/ml in severe cases
• 54% of mice (males and females) are nonproteinuric with albumin levels ranging from 2.9 to 29.7 ug/ml, similar to those in wild-type controls
• dilated medullary collecting ducts noted in nonproteinuric mice at 4 weeks of age
• podocyte foot process broadening noted in all nonproteinuric mice at 4 weeks of age
• significant decrease in podocyte number noted in both proteinuric and nonproteinuric mice at 4 weeks of age, as shown WT1 staining
• incompletely fused or fragmented GBM noted on the subendothelial side of the capillary loop in nonproteinuric mice at 4 weeks of age
• abnormal GBM thickenings with numerous subepithelial "humps" and subendothelial matrix projections noted in nonproteinuric mice at 4 weeks of age
• at 16 weeks of age, overall GBM thickness in nonproteinuric mice increases to ~100 nm more than in wild-type controls
• ectopic deposition of collagen alpha1alpha2alpha1(IV) noted in GBM humps beneath podocytes
• mesangial matrix expansion noted in mice with severe albuminuria at 4 weeks of age
• slightly increased mesangial matrix noted in nonproteinuric mice at 4 weeks of age
• glomerular crescents noted in mice with severe albuminuria at 4 weeks of age
• severely fibrotic glomeruli noted in mice with massive albuminuria at 25 weeks of age
• noted in mice with severe albuminuria at 25 weeks of age
• dilated tubules containing proteinaceous casts and cellular debris noted in mice with severe albuminuria at 25 weeks of age
• occasional dilated tubules in nonproteinuric mice at 4 weeks of age
• proteinaceous casts detected in dilated tubules of mice with severe albuminuria at 25 weeks of age
• proteinaceous casts also noted in dilated medullary collecting ducts of nonproteinuric mice at 4 weeks of age
• end-stage renal failure observed in mice with the highest levels of albuminuria

homeostasis/metabolism
• at 33-41-weeks of age, increased BUN levels are noted in association with only the highest levels of albuminuria (>1000 ug/ml)
• severely nephrotic mice show a 6-fold increase in BUN levels relative to mice with lower levels of albuminuria
• edema noted in mice with the highest levels of albuminuria
• at 4 weeks of age, mice exhibit varying levels of albuminuria ranging from no detectable albumin to >1000 ug/ml in severe cases
• 54% of mice (males and females) are nonproteinuric with albumin levels ranging from 2.9 to 29.7 ug/ml, similar to those in wild-type controls

growth/size/body
• wasting noted in mice with the highest levels of albuminuria

cardiovascular system
• dilated glomerular capillary lumen noted in mice with severe albuminuria as early as 4 weeks of age

cellular
• mesangial hypercellularity noted in mice with severe albuminuria at 4 weeks of age


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
03/18/2025
MGI 6.24
The Jackson Laboratory