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Glomerular disease

Novel candidate genes implicated in FSGS

Nature Reviews Nephrology volume 12, page 256 (2016)Cite this article

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Genetic mutations in podocyte genes can increase susceptibility to focal segmental glomerulosclerosis (FSGS), but only a small proportion of patients have been identified who have a clear genetic basis underlying their disease. A new study from Haiyang Yu and colleagues describes the development of a pipeline to detect FSGS susceptibility genes. Nine FSGS candidate genes were identified by next-generation sequencing and three were validated in vivo using a novel high-throughput method.

Next, a high-throughput method was designed to validate the candidate genes. An embryonic stem (ES) cell line was generated from FSGS-susceptible Cd2ap+/−; Synpo+/− mice, which was engineered to express a podocyte-specific doxycycline (DOX)-inducible transactivator. WNK4, KANK1, ARHGEF17, DLG5, and KAT2B were knocked down in the ES cells using shRNAs targeted specifically to the Hprt locus. KANK2 was also targeted by shRNA, as the precise mouse orthologue for KANK1 is unknown. Upon verification of shRNA targeting in vitro, mice were generated by laser-assisted microinjection of the ES cells into eight-cell embryos. Consequently, the mice were almost 100% derived from the shRNA-targeted ES cells without the need for further breeding.

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References

  1. Yu, H. et al. A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis. J. Clin. Invest. http://dx.doi.org/10.1172/JCI82592 (2016)

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  1. Jessica K. Edwards
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Edwards, J. Novel candidate genes implicated in FSGS. Nat Rev Nephrol 12, 256 (2016). https://doi.org/10.1038/nrneph.2016.30

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  • DOI: https://doi.org/10.1038/nrneph.2016.30

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