Analysis Tools
renal/urinary system
| N |
• homozygotes do not exhibit global ciliary malformations in the kidney
|
|
• homozygotes develop late-onset nephronophthisis characterized by cyst formation in the distal convoluted tubules (DCTs), cortical collecting ducts (CCDs), and glomeruli, with marked fibrosis around the renal cysts
• by P250, kidney cysts and interstitial infiltrate have replaced most of the renal parenchyma
• renal pathology is associated with increased levels of DNA damage response signaling activity, as shown by increased nuclear gammaH2AX staining in the tubular and interstitial compartments
|
kidney cyst
(
J:226661
)
|
• kidney cyst index is low at P100 but significantly increased and with marked variation at P250
|
|
• initial cyst formation occurs primarily in the cortical region, with either no or little interstitial infiltrate surrounding the dilated tubules
• cysts originate from two sites - the CCD and the DCT - at P100, with variation in tubular cyst size and amount of interstitial infiltrate
• cyst formation is progressive with enlarged cortical cysts noted at P250
• cystic CCDs do not exhibit defective cilia
|
|
• corticomedullary cysts are noted at P250
|
|
• glomerular cysts are observed at P250
|
|
• kidneys are significantly enlarged by P250
• however, kidney weight to body weight ratio is normal at P100
|
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• dedifferentiation of the corticomedullary junction is noted at P250
|
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• extensive interstitial fibrosis around the renal cysts by P250
• no collagen deposits in kidneys at P100
|
|
• gammaH2AX-positive nuclei are observed in the dilated tubules at P100
|
vision/eye
|
• abnormal rhodopsin accumulation at the photoreceptor inner segment plasma membrane and cell bodies at P30 and P100, consistent with a defect in photoreceptor protein trafficking
|
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• reduction in cone cell number at P30
|
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• progressive degeneration of photoreceptor inner segments
|
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• progressive degeneration of photoreceptor outer segments
|
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• a slight reduction of the photoreceptor layer is noted at P30 and becomes more severe at P100
• complete loss of the photoreceptor cell layer by P250
|
|
• severe reduction of the outer nuclear layer
|
|
• early-onset retinal degeneration associated with rhodopsin mislocalization in the photoreceptors and reduced cone cell numbers
|
|
• progressive decline in electroretinography wave amplitudes from P100 to P250
• both dark- and light-adapted ERGs are highly reduced in amplitude with varying degrees of loss of rod and cone function
|
nervous system
|
• abnormal rhodopsin accumulation at the photoreceptor inner segment plasma membrane and cell bodies at P30 and P100, consistent with a defect in photoreceptor protein trafficking
|
|
• reduction in cone cell number at P30
|
|
• progressive degeneration of photoreceptor inner segments
|
|
• progressive degeneration of photoreceptor outer segments
|
|
• a slight reduction of the photoreceptor layer is noted at P30 and becomes more severe at P100
• complete loss of the photoreceptor cell layer by P250
|
cellular
| N |
• mutant MEFs display normal cytoskeletal rearrangements in a wound healing assay, as shown by the % of cells with Golgi oriented towards the leading edge of the cell 24 hrs after a wound scratch
|
|
• mutant kidneys show increased nuclear gammaH2AX staining in the tubular and interstitial compartments, indicating replication stress
• gammaH2AX-positive nuclei are observed in dilated tubules at P100
• non-dilated tubules are also gammaH2AX-positive at P250, likely indicating a more general tubular stress in more fibrotic kidneys
|
homeostasis/metabolism
|
• mutant kidneys show increased nuclear gammaH2AX staining in the tubular and interstitial compartments, indicating replication stress
• gammaH2AX-positive nuclei are observed in dilated tubules at P100
• non-dilated tubules are also gammaH2AX-positive at P250, likely indicating a more general tubular stress in more fibrotic kidneys
|
growth/size/body
kidney cyst
(
J:226661
)
|
• kidney cyst index is low at P100 but significantly increased and with marked variation at P250
|
|
• initial cyst formation occurs primarily in the cortical region, with either no or little interstitial infiltrate surrounding the dilated tubules
• cysts originate from two sites - the CCD and the DCT - at P100, with variation in tubular cyst size and amount of interstitial infiltrate
• cyst formation is progressive with enlarged cortical cysts noted at P250
• cystic CCDs do not exhibit defective cilia
|
|
• corticomedullary cysts are noted at P250
|
|
• glomerular cysts are observed at P250
|
|
• kidneys are significantly enlarged by P250
• however, kidney weight to body weight ratio is normal at P100
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| nephronophthisis | DOID:12712 |
OMIM:PS256100 |
J:226661 | |
