Analysis Tools
mortality/aging
|
• homozygotes die when end-stage renal disease develops at ~14 weeks of age
|
homeostasis/metabolism
|
• blood urea nitrogen levels begin to rise at ~10 weeks, and show a 10-fold increase over wild-type levels at ~14 weeks
|
albuminuria
(
J:37963
)
|
• homozygotes develop proteinuria at ~5 weeks
• the majority of protein is of a molecular size consistent with mouse serum albumin
|
|
• as early as 2 weeks, homozygotes exhibit microhematuria which persists at relatively constant levels through the course of renal disease
|
immune system
|
• homozygotes develop progressive glomerulonephritis and die with end-stage renal disease at ~14 weeks
|
renal/urinary system
|
• at 8 weeks, homozygotes display thickened capillary walls with a rounded appearance
• by 14 weeks, half of the glomeruli are fibrotic with collapsed capillaries
|
|
• at 4 weeks, mutants show a mild expansion of mesangial cells in most glomeruli
|
albuminuria
(
J:37963
)
|
• homozygotes develop proteinuria at ~5 weeks
• the majority of protein is of a molecular size consistent with mouse serum albumin
|
|
• as early as 2 weeks, homozygotes exhibit microhematuria which persists at relatively constant levels through the course of renal disease
|
|
• homozygotes develop progressive glomerulonephritis and die with end-stage renal disease at ~14 weeks
|
|
• at end-stage, localized obliteration of podocytes is quite common
|
|
• at end-stage, pedicels are effaced
(J:37963)
• at 4 weeks, homozygotes exhibit focal swelling and obliteration of the foot processes of podocytes
(J:91619)
|
|
• by 8 weeks of age, an abundance of epithelial cell microvilli are observed
|
|
• the mutant GBM displays focal multilaminated thickening and thinning, beginning in the external capillary loops at 4 weeks and extending throughout the GBM by 8 weeks
|
|
• at 4 weeks, mutants show a mild expansion of mesangial matrix in most glomeruli
• by end-stage, the mesangial matrix is grossly expanded and fibrotic
|
|
• by 14 weeks, half of the glomeruli are fibrotic
|
small kidney
(
J:37963
)
|
• by end-stage, the mutant kidney is 30-50% smaller by mass than that of wild-type mice
|
|
• at end-stage, the mutant kidney has a rough granular appearance
|
pale kidney
(
J:37963
)
|
• at end-stage, the mutant kidney is pale
|
vision/eye
|
• in contrast to Alport patients, homozygotes do NOT display lenticonus; however, the interior layer of the basement membrane encasing the anterior lens is irregular instead of smooth
|
hearing/vestibular/ear
|
• COL4A5 chain is absent from all cochlear basement membranes except those in the vessels of the stria vascularis; in contrast, expression of COL4A1 and COL4A2 chains is unchanged
• homozygotes show significant thinning of the basement membrane running from the spiral limbus, down the inner sulcus, across the basilar membrane and up to the spiral prominence
• basement membranes that normally ensheathe the root cells are not detectable
• basement membranes surrounding the strial vessels are significantly thickened, with some degree of variation
• a greater abundance of COL4A1 and 4A2 chains and entactin is noted in strial basement membranes
|
|
• homozygotes exhibit absence of the COL4A3 and COL4A4 chains throughout the membranous labyrinth
|
|
• basement membranes surrounding the strial vessels are significantly thickened, with some degree of variation
• at 5 weeks, mutant strial basement membranes are 1.6-3.1 thicker than normal, indicating that ultrastructural changes occur prior to the onset of uremia at ~12 weeks
• a greater abundance of COL4A1 and 4A2 chains and entactin is noted in strial basement membranes
|
|
• endothelial cells lining the strial vessels are swollen and contain numerous vacuoles, resulting in capillaries with reduced internal diameters
|
|
• homozygotes show variable changes in strial marginal cells, associated with enlarged, more rounded nuclei
• at 12-14 weeks, ~50% of mice with advanced glomerulonephritis show a reduction or loss of marginal cell basolateral infoldings
|
cardiovascular system
|
• at 8 weeks, homozygotes display thickened capillary walls with a rounded appearance
• by 14 weeks, half of the glomeruli are fibrotic with collapsed capillaries
|
|
• endothelial cells lining the strial vessels are swollen and contain numerous vacuoles, resulting in capillaries with reduced internal diameters
|
cellular
|
• at 4 weeks, mutants show a mild expansion of mesangial cells in most glomeruli
|
|
• COL4A5 chain is absent from all cochlear basement membranes except those in the vessels of the stria vascularis; in contrast, expression of COL4A1 and COL4A2 chains is unchanged
• homozygotes show significant thinning of the basement membrane running from the spiral limbus, down the inner sulcus, across the basilar membrane and up to the spiral prominence
• basement membranes that normally ensheathe the root cells are not detectable
• basement membranes surrounding the strial vessels are significantly thickened, with some degree of variation
• a greater abundance of COL4A1 and 4A2 chains and entactin is noted in strial basement membranes
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| autosomal recessive Alport syndrome | DOID:0110033 |
OMIM:203780 |
J:37963 | |
