Analysis Tools
mortality/aging
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• most homozygotes die 3 weeks after birth
(J:37017)
• only ~5% of homozygotes survive beyond 4 months of age
(J:37017)
• mice do not survive beyond 32 weeks
(J:207595)
|
renal/urinary system
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• relative levels of urinary protein are similar in mutant and wild-type mice until ~P40, then rise many-fold in mutant mice
(J:37017)
• notably, homozygotes do NOT exhibit hematuria
(J:37017)
|
albuminuria
(
J:37017
)
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• predominant protein detected in urine is albumin
|
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• at P>65, mutant kidneys appear mottled and wrinkled
• however, at ~5 weeks, mutant kidneys are still externally normal with only minor histological alterations relative to wild-type
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• at P40, a few glomeruli exhibit patches of thickened, closed capillary loops
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• homozygotes exhibit late-onset, progressive glomerulonephritis, leading to renal failure
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• homozygotes exhibit a basket-weave thickening and lamellation of the glomerular basal lamina (BL)
(J:37017)
• several changes in the molecular composition of BL are observed; some occur as early as P15
(J:37017)
• decellularized glomerulus basement membrane with a rough and blebby surface
(J:207595)
|
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• basket-weave thickening of the glomerular basal lamina
(J:37017)
• diffuse
(J:207595)
|
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• at P40, homozygotes display accumulation of interstitial cells and extracellular matrix
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• at P40, a few glomeruli exhibit retricted segments of thickened Bowman's capsule (crescents) and/or patches of thickened, closed capillary loops (segmental glomerulosclerosis)
(J:37017)
• both the number of glomeruli affected and the severity of glomerulosclerotic defects rise subsequently
(J:37017)
|
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• at P40, a few glomeruli exhibit retricted segments of thickened Bowman's capsule (crescents)
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small kidney
(
J:37017
)
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• at P>65, mutant kidneys appear small relative to wild-type
|
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• at P40, homozygotes display atrophic kidney tubules
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renal cast
(
J:207595
)
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• tubular protein cast
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• homozygotes display impaired glomerular filtration leading to uremia
|
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• late-onset, progressive glomerulonephritis leading to renal failure
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homeostasis/metabolism
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• in homozygotes, blood creatinine levels rise after P60
• in contrast, creatinine concentrations in urine decline after P60
• a small % of mutants maintain normal levels of blood creatinine and show a mild renal phenotype
|
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• in homozygotes, blood urea nitrogen levels rise after P60, indicating compromised glomerular filtration
• in contrast, urea nitrogen concentrations in urine decline after P60, suggesting a tubular dysfunction
• notably, a small % of homozygotes maintain normal levels of blood urea as late as P100, and exhibit only a mild renal pathology
|
|
• relative levels of urinary protein are similar in mutant and wild-type mice until ~P40, then rise many-fold in mutant mice
(J:37017)
• notably, homozygotes do NOT exhibit hematuria
(J:37017)
|
albuminuria
(
J:37017
)
|
• predominant protein detected in urine is albumin
|
behavior/neurological
growth/size/body
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• at 2-3 months, most homozygotes begin to loose weight
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hearing/vestibular/ear
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• variable penetrance; 3 out of 12 pairs of mutants analyzed showed significantly increased auditory thresholds relative to wild-type
• other mutants showed hearing within normal ranges of thresholds and sensitivities, suggesting that the hearing loss may be due to genetic background differences
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immune system
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• homozygotes exhibit late-onset, progressive glomerulonephritis, leading to renal failure
|
cardiovascular system
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• at P40, a few glomeruli exhibit patches of thickened, closed capillary loops
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| autosomal recessive Alport syndrome | DOID:0110033 |
OMIM:203780 |
J:37017 , J:207595 | |
