Analysis Tools
mortality/aging
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• mice surviving past the perinatal stage die by several months of age
|
|
• fewer homozygous mice are born than expected (about 10% rather than 25%)
• in lethal embryos and neonates, no gross or histological abnormalities are noted
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growth/size/body
weight loss
(
J:83911
)
|
• weight loss beginning after ~6 weeks of age
|
|
• growth rate of homozygotes begins to slow at ~6 weeks of age
|
renal/urinary system
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• areas of glomerular capillary collapse in some homozygous mice at 4 weeks of age
|
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• in a cell culture system, differentiated mutant podocytes are less adherent than wild-type cells to GBM components collagen IV (2.7-fold decrease) and laminin 10/11 (3.1-fold decrease)
• when subjected to high shear stress via fluid flow, mutant podocytes are markedly less adherent to a collagen I substrate than rescued podocytes stably transfected with Actn4-GFP; the % of mutant cells remaining adherent after flow is 6.5% versus 80% for rescued cells, with mutant cells detaching at a lower shear stress than rescued cells
• in response to an applied force, mutant podocytes exhibit 4-fold more bead displacement than wild-type cells by magnetic pulling cytometry, suggesting weaker integrin-cytoskeleton linkages
• decreased podocyte adhesion is not due to changes in cell death or proliferation
|
|
• podocyte markers detected in urine as early as 8 days of age, indicating podocyte detachment in vivo
• urinary WT1 protein detected in 75% and 83% of homozygous mice at 1 week and at 6-10 weeks of age, respectively, never seen in wild-type controls
• urinary podocin detected in a subset of urine samples
• all mice exhibiting podocyturia show some degree of proteinuria and vice versa
|
|
• increasing albuminuria with advancing age
(J:83911)
• significantly increased albumin/creatinine ratios both at 1-2 weeks and at 6-10 weeks of age, unlike in wild-type controls
(J:118122)
• podocyturia and albuminuria appear to develop concurrently
(J:118122)
|
|
• mild microalbuminuria in most but not all homozygous mice at sacrifice (5.5 weeks of age)
|
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• mild disruption of podocyte structure with areas of focal foot process effacement at 10 days of age
• more extensive foot process effacement by 10 weeks of age
• however, slit diaphragms appear normal
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• podocyte number per glomerulus is decreased by 9.9% at 8-9 days of age, and by 18.8% at 6-10 weeks of age
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• areas with duplications ("blebs") on the subepithelial aspect of the GBM in some mice at 5 weeks of age
|
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• evidence of focal and segmental glomerulosclerosis in most homozygous mice by 10 weeks of age
|
small kidney
(
J:83911
)
|
• kidneys are typically small by 10 weeks of age
|
|
• dilated tubules with disrupted architecture by 10 weeks of age
|
renal cast
(
J:83911
)
|
• dilated tubules are filled with proteinaceous material by 10 weeks of age
|
pale kidney
(
J:83911
)
|
• kidneys are typically pale by 10 weeks of age
|
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• eventual kidney failure
|
homeostasis/metabolism
|
• increased BUN levels in many but not all homozygous mice at 5.5 weeks of age
|
|
• increasing albuminuria with advancing age
(J:83911)
• significantly increased albumin/creatinine ratios both at 1-2 weeks and at 6-10 weeks of age, unlike in wild-type controls
(J:118122)
• podocyturia and albuminuria appear to develop concurrently
(J:118122)
|
|
• mild microalbuminuria in most but not all homozygous mice at sacrifice (5.5 weeks of age)
|
cellular
|
• in a cell culture system, differentiated mutant podocytes are less adherent than wild-type cells to GBM components collagen IV (2.7-fold decrease) and laminin 10/11 (3.1-fold decrease)
• when subjected to high shear stress via fluid flow, mutant podocytes are markedly less adherent to a collagen I substrate than rescued podocytes stably transfected with Actn4-GFP; the % of mutant cells remaining adherent after flow is 6.5% versus 80% for rescued cells, with mutant cells detaching at a lower shear stress than rescued cells
• in response to an applied force, mutant podocytes exhibit 4-fold more bead displacement than wild-type cells by magnetic pulling cytometry, suggesting weaker integrin-cytoskeleton linkages
• decreased podocyte adhesion is not due to changes in cell death or proliferation
|
|
• podocyte markers detected in urine as early as 8 days of age, indicating podocyte detachment in vivo
• urinary WT1 protein detected in 75% and 83% of homozygous mice at 1 week and at 6-10 weeks of age, respectively, never seen in wild-type controls
• urinary podocin detected in a subset of urine samples
• all mice exhibiting podocyturia show some degree of proteinuria and vice versa
|
|
• significant increase in baseline and SDF-1-induced lymphocyte chemotaxis relative to wild-type controls
|
cardiovascular system
|
• areas of glomerular capillary collapse in some homozygous mice at 4 weeks of age
|
immune system
|
• significant increase in baseline and SDF-1-induced lymphocyte chemotaxis relative to wild-type controls
|
hematopoietic system
|
• significant increase in baseline and SDF-1-induced lymphocyte chemotaxis relative to wild-type controls
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| focal segmental glomerulosclerosis 1 | DOID:0111128 |
OMIM:603278 |
J:83911 | |
