Analysis Tools|
Allele Symbol Allele Name Allele ID |
Six2tm1(tTA,tetO-EGFP/cre)Amc targeted mutation 1, Andrew P McMahon MGI:3845218 |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Summary |
15 genotypes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are viable, fertile, and display no obvious abnormalities
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some of the few proximal tubules present are cystic
|
|
• developmental defects are similar to mutants wild-type for Wwtr1
|
|
• some of the few proximal tubules present are cystic
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Nephrogenesis abnormalities in Wwtr1tm1Hmc/Wwtr1tm1Hmc Six2tm1(tTA,tetO-EGFP/cre)Amc/Six2+, Yap1tm1Hmc/Yap1tm1Hmc Six2tm1(tTA,tetO-EGFP/cre)Amc/Six2+ and double mutant mice
|
• spotty hemorrhages are seen at P0
|
|
• highly cystic tubules in the cortex at P0
|
|
• spotty hemorrhages are seen at P0
|
|
• highly cystic tubules in the cortex at P0
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2-3 month-old mice exhibit polydipsia
|
|
• mice excrete more glucose in urine
|
|
• mice excrete more phosphate in urine
|
|
• mice excrete more glucose in urine
|
|
• mice excrete more phosphate in urine
|
|
• adult kidney is disorganized
|
|
• kidneys show a defect in proximal tubule formation
• marker analysis indicates that formation of differentiated proximal tubule cells is impaired
• however, presumptive proximal tubule formation is not altered and formation of podocytes, loops of Henle, and distal tubules are not affected
|
|
• in adults
|
|
• adult kidney contains fewer proximal tubules
• decrease in number of proximal tubule cells
|
|
• kidneys show calcium accumulation in renal tubules at 2 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Fanconi syndrome | DOID:1062 |
OMIM:PS134600 |
J:266356 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Abnormal kidney development in Yap1tm1Hmc/Yap1tm1Hmc Six2tm1(tTA,tetO-EGFP/cre)Amc/Six2+ mice
|
• die within 48 hours of birth
|
|
• convoluted tubules are not distinguishable in the inner cortex at E18.5
|
|
• seen at P0
|
|
• few detectable glomeruli
|
|
• few detectable glomeruli
|
|
• limited nephrogenesis with abnormal morphogenesis of S shaped bodies at E13.5
• dramatic decrease in the number of nascent nephrons (pretubular aggregates, comma shaped bodies, S shaped bodies, and renal vesicles) at E14.5
|
|
• abnormal morphogenesis of S shaped bodies at E13.5
• dramatic decrease in the number of nascent nephrons (pretubular aggregates, comma shaped bodies, S shaped bodies, and renal vesicles) at E14.5
• dramatic decrease in the number of cap mesenchyme derived structures that reach the S shaped bodies
• at E14.5 the connecting segment where the S shaped body connects to the ureteric epithelium is abnormal and the distal segment fails to correctly merge with the outermost edge of the ureteric bud
• slight reduction in proliferation in the proximal part of the renal vesicle and the distal part of the S shaped bodies
|
|
• reduced nephrogenic zone at E18.5
|
|
• the medulla is mainly composed of collecting ducts at E18.5 suggesting a decrease in the formation of loops of Henle
|
|
• small papilla at E18.5
|
|
• at P0
|
|
• convoluted tubules are not distinguishable in the inner cortex at E18.5
|
|
• defects in formation
|
|
• few detectable proximal tubules are present
|
|
• few detectable proximal tubules are present
|
|
• decrease in the number of ureteric bud tips at E16.5 and P0 but not at E14.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice begin to die after weaning with all mice dying before 8 weeks of age and a median survival of 33.3 days
|
|
• a cavity appears at P14 and expands with age
• however, BMP inhibition rescues kidney defects
|
|
• at P28
|
|
• progressive loss of nephron components, including glomeruli, proximal and distal tubules, and the loop of Henle located in the cortex and outer medullary regions
|
|
• fewer glomeruli at P7 and P14
|
|
• reduced number of tubules at P21
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Kidney abnormalities in Cdc42tm1Brak/Cdc42tm1Brak Six2tm1(tTA,tetO-EGFP/cre)Amc/Six2+ mice
|
• absence of convoluted renal epithelia and glomeruli in the cortex
|
|
• at P0
|
|
• very limited nephrogenesis
|
|
• reduced nephrogenic zone at E18.5
|
|
• small papilla at E18.5
|
|
• at P0
|
|
• tubules are decreased in number, truncated and have barely discernible lumens
|
|
• fewer proximal tubules
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Hypoplasia and loss of glomeruli and proximal tubules in Wasltm2Sbs/Wasltm2Sbs Six2tm1(tTA,tetO-EGFP/cre)Amc/Six2+ kidneys
|
• decrease in proximal tubule numbers at P0
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased mesangial cell proliferation at 12 weeks of age
|
|
• podocyte detachment at 12 weeks of age
|
|
• progressive albuminuria, starting at 6 weeks after birth
• however, no increase in proteinuria is detected at birth
|
|
• TEM analysis showed pronounced widening and misconfiguration (effacement) of podocyte foot processes at 8 and 12 weeks of age
• 3D SIM microscopy showed reduced filtration slit density (FSD), indicating aberrant foot process architecture at 8 weeks of age
• SEM revealed marked simplification, reduced branching, and misconfiguration of podocyte foot processes
|
|
• marked rarefaction and loss of slit diaphragms at 12 weeks of age
|
|
• progressive podocyte loss
|
|
• mesangial sclerosis at 12 weeks of age
|
|
• mice develop a nephrotic syndrome with a late-onset focal segmental glomerulosclerosis (FSGS)-like phenotype in adulthood
• a significantly increased glomerulosclerosis score is noted at 8 and 12 weeks of age
|
|
• tubular dilation at 12 weeks of age
|
|
• formation of proteinaceous casts at 12 weeks of age
|
|
• progressive loss of filtration-barrier function, starting at 6 weeks after birth
|
|
• increased mesangial cell proliferation at 12 weeks of age
|
|
• podocyte detachment at 12 weeks of age
|
|
• progressive albuminuria, starting at 6 weeks after birth
• however, no increase in proteinuria is detected at birth
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| focal segmental glomerulosclerosis | DOID:1312 |
OMIM:PS603278 |
J:333727 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die in the neonatal period
|
| N |
• mice show no obvious defects in nephron lumen formation or luminal continuity indicating normal early stages of nephrogenesis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit overproduction of a proximal tubule marker
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die shortly after birth
|
|
• multiple
|
|
• at E14.5, kidneys exhibit a thin cortical nephrogenic zone and poor nephron development
• mice exhibit depletion of nephron progenitors and premature tubule formation
• at E12.5, ectopic tubules are observed dorsal to the poorly branched ureteric bud-derived epithelia
|
|
• at E14.5, kidneys lack condensed metanephric mesenchyme around the ureteric buds in the cortex and contain few Pax2+ scattered tubules
|
|
• at E14.5, no ureteric bud-derived epithelia are observed in the mutant cortex
|
|
• thin cortical nephrogenic zone at E14.5
|
|
• at E14.5
• severe at birth
|
|
• some of the dilated tubules are positive for a proximal tubule marker
• however, proximal tubules are not overproduced
|
|
• at E14.5, ureteric bud branching is impaired
|
|
• multiple
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• apoptotic cells in the nephron as early as P7
|
|
• apoptotic cells in the nephron as early as P7
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
||
|
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support. |
last database update 12/17/2024 MGI 6.24 |
|
|
|
||
