Analysis Tools
renal/urinary system
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• glomerular cysts first develop at 3 months of age; they are distributed throughout the cortex area and are characterized by enlarged Bowmans space lined by flattened PECs and retracted capillary tufts
• % of glomeruli with cystic changes is significantly increased at 6 months
• at 12 months, glomerular cysts appear slightly but significantly larger in heterozygous kidneys
• however, glomerulotubular junction is preserved in glomeruli with cystic change
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• mild but significant increase in urine albumin/creatinine ratio at 6 and 12 months of age
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albuminuria
(
J:240798
)
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• at P0, mean urinary albumin concentration is 141.1 +/- 129.4 mg/l versus 34.6 +/- 7.8 in wild-type controls
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• numerous urinary dysmorphic erythrocytes found at P0, suggestive of glomerular origin
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• glomerular parietal epithelial cells (PECs) show an activated phenotype (overexpression of claudin-1 and induction of CD44), induction of DDR1 (discoidin domain receptors 1), and activation of integrin-linked kinase (ILK) pathway at 1 month of age, prior to the development of glomerular cysts and periglomerular inflammation
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• at 1 month of age, PECs in a subset (~15%) of glomeruli appear cube-shaped with enlarged nuclei, instead of forming a monolayer of thin epithelial cells with flat nuclei as in normal PECs
• cuboidal PECs lining the Bowman's capsule are found in about one-third of non-cystic glomeruli at 6 and 12 months of age
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• integrin-linked kinase (ILK) expression is strongly enhanced in podocytes at 1 and 6 months of age
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• reduced podocyte foot process formation at P0
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• expression of nephrin is dramatically reduced in glomeruli at P0; although occasionally detected in slit diaphragms, nephrin is abnormally localized in cytoplasmic vacuoles (vesicles) within the podocytes
• in contrast, podocin is normally expressed in the basal region of the podocytes along the GBM
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• glomerulus basement membrane duplication at P0
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• integrin-linked kinase (ILK) expression is strongly enhanced in the mesangium at 1 and 6 months of age
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• cytoplasmic vacuoles that stain positively with anti-albumin antibody in proximal tubular sections at P0
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• in situ gelatin zymography revealed enhanced matrix metalloproteinase (MMP) enzymatic activity in the periglomerular region and around the renal tubules at 6 months of age
• pretreatment of renal tissue with EDTA, a specific inhibitor of MMP2 and MMP9, blocked gelanolytic activity
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• inflammatory infiltrates are first detected in the kidney at 3 months of age
• at 12 months of age, periglomerular and perivascular inflammatory infiltrates are mostly composed by T-lymphocytes surrounded by macrophages
• however, no significant fibrosis is noted, except in inflammatory areas, and tubules remain normal at 12 months
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homeostasis/metabolism
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• mild but significant increase in urine albumin/creatinine ratio at 6 and 12 months of age
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albuminuria
(
J:240798
)
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• at P0, mean urinary albumin concentration is 141.1 +/- 129.4 mg/l versus 34.6 +/- 7.8 in wild-type controls
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• numerous urinary dysmorphic erythrocytes found at P0, suggestive of glomerular origin
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immune system
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• inflammatory infiltrates are first detected in the kidney at 3 months of age
• at 12 months of age, periglomerular and perivascular inflammatory infiltrates are mostly composed by T-lymphocytes surrounded by macrophages
• however, no significant fibrosis is noted, except in inflammatory areas, and tubules remain normal at 12 months
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cardiovascular system
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• adults exhibit retinal tortuosity
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• newborns exhibit brain hemorrhages
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muscle
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• adults exhibit muscular dystrophy
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nervous system
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• newborns exhibit brain hemorrhages
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vision/eye
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• adults exhibit retinal tortuosity
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growth/size/body
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• glomerular cysts first develop at 3 months of age; they are distributed throughout the cortex area and are characterized by enlarged Bowmans space lined by flattened PECs and retracted capillary tufts
• % of glomeruli with cystic changes is significantly increased at 6 months
• at 12 months, glomerular cysts appear slightly but significantly larger in heterozygous kidneys
• however, glomerulotubular junction is preserved in glomeruli with cystic change
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| kidney disease | DOID:557 | J:240798 | ||
