Analysis Tools
growth/size/body
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• proximal tubule cysts at E17.5
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• large glomerular cysts at E17.5
• however, glomerular architecture is largely normal in cystic glomeruli
• no obvious misorganization is noted in glomeruli, either pre- or post-cyst formation
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mortality/aging
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• only a few mutant mice survive to weaning age
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renal/urinary system
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• 91% of E17.5 embryos display severe kidney defects including hypoplastic kidneys with glomerular cysts (hypodysplastic kidneys)
• however, nephrogenesis is normal and no ureter obstruction is observed at E17.5
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• whereas primary cilia appear normal in E17.5 glomeruli, both the number of ciliated cells and the average length of cilia are severely reduced in proximal tubules at E14.5
• defect in cilia elongation is noted in both S-shaped bodies and E14.5 proximal tubules, suggesting that impaired cilium formation precedes cystogenesis
• defect in cilia number and length is due to impaired axoneme extension rather than abnormal basal body migration or positioning
• ciliogenesis defects in proximal tubules are associated with markedly increased RhoGTPase-dependent F-actin polymerization around the basal body
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• proximal tubule cysts at E17.5
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• large glomerular cysts at E17.5
• however, glomerular architecture is largely normal in cystic glomeruli
• no obvious misorganization is noted in glomeruli, either pre- or post-cyst formation
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• significant dilation of Bowman's capsule at E17.5
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• E17.5 kidneys exhibit hypoplasia or agenesis
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• defect in cilia elongation is noted in S-shaped bodies at E17.5
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• occasional proximal tubule dilation at E17.5
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• E17.5 kidneys exhibit hypoplasia or agenesis
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nervous system
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• 54% of E17.5 embryos display neural tube closure defects (exencephaly and spina bifida)
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spina bifida
(
J:232342
)
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• at E17.5
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exencephaly
(
J:232342
)
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• at E17.5
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embryo
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• 54% of E17.5 embryos display neural tube closure defects (exencephaly and spina bifida)
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spina bifida
(
J:232342
)
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• at E17.5
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cellular
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• upon serum withdrawal, less than 20% mouse embryonic fibroblasts (MEFs) produce elongated cilia versus ~60% of wild-type MEFs, and cilia that do form are on average half the length of wild-type cilia
• defects in MEF cilia number and length can be rescued by introduction of full-length wild-type but not the L1396Q mutant protein
• ciliary defects in mutant MEFs are fully rescued by ROCK1/2 and F-actin inhibition but only partially rescued by Rac1 inhibition
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• whereas primary cilia appear normal in E17.5 glomeruli, both the number of ciliated cells and the average length of cilia are severely reduced in proximal tubules at E14.5
• defect in cilia elongation is noted in both S-shaped bodies and E14.5 proximal tubules, suggesting that impaired cilium formation precedes cystogenesis
• defect in cilia number and length is due to impaired axoneme extension rather than abnormal basal body migration or positioning
• ciliogenesis defects in proximal tubules are associated with markedly increased RhoGTPase-dependent F-actin polymerization around the basal body
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