Analysis Tools
renal/urinary system
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• male mice exhibit significantly higher urinary levels of glutamic acid, glutamine, methionine, pipecolic acid, proline, and cysteine than wild-type males at 24 weeks of age
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cystinuria
(
J:349712
)
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• at 24 weeks of age
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• at 24 weeks of age
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prolinuria
(
J:349712
)
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• at 24 weeks of age
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• male, but not female, mice show significantly higher urinary glucose-to-creatinine ratios (GCR) at 20 and 24 weeks of age
• however, male nonfasting plasma glucose levels are normal at 24 weeks of age
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• male mice show a significantly higher urinary potassium-to-creatinine ratio (KCR) at 24 weeks of age
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• male mice show a significantly higher urinary phosphate-to-creatinine ratio (PhosCR) at 24 weeks of age
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• male mice show significantly higher urinary levels of HAVCR1 (also known as kidney injury molecule 1 or KIM-1) than wild-type males at 16 weeks of age, suggesting impaired proximal tubule function
• a subset of females also show an increase in urinary HAVCR1 levels relative to wild-type females
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albuminuria
(
J:349712
)
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• male, but not female, mice show a significantly higher urinary albumin-to-creatinine ratio (ACR) than wild-type males at 24 weeks of age
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• although membrane receptor abundance is relatively normal, male kidneys show distorted receptor polarization and brush border organization in proximal tubule cells
• LRP2/Megalin-positive tubular clusters appear more disorganized and show a reduced apical concentration or a more jagged appearance
• ACE2 is strikingly nonpolarized with an apical-to-cytoplasmic polarity ratio of 1:1 versus nearly 3:1 in wild-type samples
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• proximal tubules exhibit a more diffuse wheat germ agglutinin (WGA) staining, whereas wild-type samples show strong WGA staining near the apical regions of proximal tubules
• proximal tubule brush borders show reduced apical intensities of LRP2/Megalin and WGA, an extreme loss of ACE2 polarization, and erratic actin localization
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• male mice exhibit proximal tubule reabsorption defects
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homeostasis/metabolism
| N |
• female mice show normal urinary albumin- and glucose-to-creatinine ratios at 24 weeks of age
• male mice show normal urinary sodium-, chloride- and calcium-to-creatinine ratios at 24 weeks of age
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• although immature LC3-I and GABARAP-I levels are relatively normal, male kidneys show a 3-fold increase in the amount of the mature lipidated form of the autophagosomal protein (LC3-II) and a significantly higher LC3 II:I ratio than wild-type male kidneys, indicating altered autophagy
• mouse embryonic fibroblasts (MEFs) derived from male mice show significantly more SQSTM1/p62 than control MEFs
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• male MEFs treated with chloroquine (to inhibit lysosomal degradation) show more diffuse and smaller LC3- and GABARAP-positive structures with little actin recruited to autophagosomal membranes, indicating altered autophagosome organization and actin assembly
• MEFs exposed to the autophagy-inducing mTOR inhibitor rapamycin fail to effectively shape GABARAP-associated autophagic membranes into discrete puncta, indicating defects in autophagic membrane morphogenesis
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|
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• male mice exhibit significantly higher urinary levels of glutamic acid, glutamine, methionine, pipecolic acid, proline, and cysteine than wild-type males at 24 weeks of age
|
cystinuria
(
J:349712
)
|
|
• at 24 weeks of age
|
|
|
• at 24 weeks of age
|
prolinuria
(
J:349712
)
|
|
• at 24 weeks of age
|
|
|
• male, but not female, mice show significantly higher urinary glucose-to-creatinine ratios (GCR) at 20 and 24 weeks of age
• however, male nonfasting plasma glucose levels are normal at 24 weeks of age
|
|
|
• male mice show a significantly higher urinary potassium-to-creatinine ratio (KCR) at 24 weeks of age
|
|
|
• male mice show a significantly higher urinary phosphate-to-creatinine ratio (PhosCR) at 24 weeks of age
|
|
• male mice show significantly higher urinary levels of HAVCR1 (also known as kidney injury molecule 1 or KIM-1) than wild-type males at 16 weeks of age, suggesting impaired proximal tubule function
• a subset of females also show an increase in urinary HAVCR1 levels relative to wild-type females
|
albuminuria
(
J:349712
)
|
|
• male, but not female, mice show a significantly higher urinary albumin-to-creatinine ratio (ACR) than wild-type males at 24 weeks of age
|
cellular
|
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• male kidney proximal tubules exhibit a less polarized and more disorganized actin localization than wild-type tubules
|
|
|
• although immature LC3-I and GABARAP-I levels are relatively normal, male kidneys show a 3-fold increase in the amount of the mature lipidated form of the autophagosomal protein (LC3-II) and a significantly higher LC3 II:I ratio than wild-type male kidneys, indicating altered autophagy
• mouse embryonic fibroblasts (MEFs) derived from male mice show significantly more SQSTM1/p62 than control MEFs
|
|
|
• male MEFs treated with chloroquine (to inhibit lysosomal degradation) show more diffuse and smaller LC3- and GABARAP-positive structures with little actin recruited to autophagosomal membranes, indicating altered autophagosome organization and actin assembly
• MEFs exposed to the autophagy-inducing mTOR inhibitor rapamycin fail to effectively shape GABARAP-associated autophagic membranes into discrete puncta, indicating defects in autophagic membrane morphogenesis
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Fanconi syndrome | DOID:1062 |
OMIM:PS134600 |
J:349712 | |
