Sprouty1 haploinsufficiency prevents renal agenesis in a model of Fraser syndromeCitation formats

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Sprouty1 haploinsufficiency prevents renal agenesis in a model of Fraser syndrome. / Pitera, Jolanta E.; Woolf, Adrian S.; Albert Basson, M.; Scambler, Peter J.

In: Journal of the American Society of Nephrology, Vol. 23, No. 11, 31.10.2012, p. 1790-1796.

Research output: Contribution to journalArticle

Harvard

Pitera, JE, Woolf, AS, Albert Basson, M & Scambler, PJ 2012, 'Sprouty1 haploinsufficiency prevents renal agenesis in a model of Fraser syndrome' Journal of the American Society of Nephrology, vol. 23, no. 11, pp. 1790-1796. https://doi.org/10.1681/ASN.2012020146

APA

Pitera, J. E., Woolf, A. S., Albert Basson, M., & Scambler, P. J. (2012). Sprouty1 haploinsufficiency prevents renal agenesis in a model of Fraser syndrome. Journal of the American Society of Nephrology, 23(11), 1790-1796. https://doi.org/10.1681/ASN.2012020146

Vancouver

Pitera JE, Woolf AS, Albert Basson M, Scambler PJ. Sprouty1 haploinsufficiency prevents renal agenesis in a model of Fraser syndrome. Journal of the American Society of Nephrology. 2012 Oct 31;23(11):1790-1796. https://doi.org/10.1681/ASN.2012020146

Author

Pitera, Jolanta E. ; Woolf, Adrian S. ; Albert Basson, M. ; Scambler, Peter J. / Sprouty1 haploinsufficiency prevents renal agenesis in a model of Fraser syndrome. In: Journal of the American Society of Nephrology. 2012 ; Vol. 23, No. 11. pp. 1790-1796.

Bibtex

@article{61d242a29f8c4561819a8d6a552b4feb,
title = "Sprouty1 haploinsufficiency prevents renal agenesis in a model of Fraser syndrome",
abstract = "Deficiency of the extracellular matrix molecule FRAS1, normally expressed by the ureteric bud, leads to bilateral renal agenesis in humans with Fraser syndrome and blebbed (Fras1bl/bl) mice. The metanephric mesenchyme of these mutants fails to express sufficient Gdnf, which activates receptor tyrosine kinase (RTK) signalling, contributing to the phenotype. To determine whether modulating RTK signalling may overcome the abnormal nephrogenesis characteristic of Fraser syndrome, we introduced a single null Sprouty1 allele into Fras1bl/bl mice, thereby reducing the ureteric bud's expression of this anti-branching molecule and antagonist of RTK signalling. This prevented renal agenesis in Fras1bl/bl mice, permitting kidney development and postnatal survival. We found that fibroblast growth factor (FGF) signalling contributed to this genetic rescue, and exogenous FGF10 rescued defects in Fras1bl/bl rudiments in vitro . Whereas wild-type metanephroi expressed FRAS1 and the related proteins FREM1 and FREM2, FRAS1 was absent and the other proteins were downregulated in rescued kidneys, consistent with a reciprocally stabilized FRAS1/FREM1/FREM2 complex. In addition to contributing to knowledge regarding events during nephrogenesis, the demonstrated rescue of renal agenesis in a model of a human genetic disease raises the possibility that enhancing growth factor signaling might be a therapeutic approach to ameliorate this devastating malformation. Copyright {\circledC} 2012 by the American Society of Nephrology.",
author = "Pitera, {Jolanta E.} and Woolf, {Adrian S.} and {Albert Basson}, M. and Scambler, {Peter J.}",
year = "2012",
month = "10",
day = "31",
doi = "10.1681/ASN.2012020146",
language = "English",
volume = "23",
pages = "1790--1796",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "11",

}

RIS

TY - JOUR

T1 - Sprouty1 haploinsufficiency prevents renal agenesis in a model of Fraser syndrome

AU - Pitera, Jolanta E.

AU - Woolf, Adrian S.

AU - Albert Basson, M.

AU - Scambler, Peter J.

PY - 2012/10/31

Y1 - 2012/10/31

N2 - Deficiency of the extracellular matrix molecule FRAS1, normally expressed by the ureteric bud, leads to bilateral renal agenesis in humans with Fraser syndrome and blebbed (Fras1bl/bl) mice. The metanephric mesenchyme of these mutants fails to express sufficient Gdnf, which activates receptor tyrosine kinase (RTK) signalling, contributing to the phenotype. To determine whether modulating RTK signalling may overcome the abnormal nephrogenesis characteristic of Fraser syndrome, we introduced a single null Sprouty1 allele into Fras1bl/bl mice, thereby reducing the ureteric bud's expression of this anti-branching molecule and antagonist of RTK signalling. This prevented renal agenesis in Fras1bl/bl mice, permitting kidney development and postnatal survival. We found that fibroblast growth factor (FGF) signalling contributed to this genetic rescue, and exogenous FGF10 rescued defects in Fras1bl/bl rudiments in vitro . Whereas wild-type metanephroi expressed FRAS1 and the related proteins FREM1 and FREM2, FRAS1 was absent and the other proteins were downregulated in rescued kidneys, consistent with a reciprocally stabilized FRAS1/FREM1/FREM2 complex. In addition to contributing to knowledge regarding events during nephrogenesis, the demonstrated rescue of renal agenesis in a model of a human genetic disease raises the possibility that enhancing growth factor signaling might be a therapeutic approach to ameliorate this devastating malformation. Copyright © 2012 by the American Society of Nephrology.

AB - Deficiency of the extracellular matrix molecule FRAS1, normally expressed by the ureteric bud, leads to bilateral renal agenesis in humans with Fraser syndrome and blebbed (Fras1bl/bl) mice. The metanephric mesenchyme of these mutants fails to express sufficient Gdnf, which activates receptor tyrosine kinase (RTK) signalling, contributing to the phenotype. To determine whether modulating RTK signalling may overcome the abnormal nephrogenesis characteristic of Fraser syndrome, we introduced a single null Sprouty1 allele into Fras1bl/bl mice, thereby reducing the ureteric bud's expression of this anti-branching molecule and antagonist of RTK signalling. This prevented renal agenesis in Fras1bl/bl mice, permitting kidney development and postnatal survival. We found that fibroblast growth factor (FGF) signalling contributed to this genetic rescue, and exogenous FGF10 rescued defects in Fras1bl/bl rudiments in vitro . Whereas wild-type metanephroi expressed FRAS1 and the related proteins FREM1 and FREM2, FRAS1 was absent and the other proteins were downregulated in rescued kidneys, consistent with a reciprocally stabilized FRAS1/FREM1/FREM2 complex. In addition to contributing to knowledge regarding events during nephrogenesis, the demonstrated rescue of renal agenesis in a model of a human genetic disease raises the possibility that enhancing growth factor signaling might be a therapeutic approach to ameliorate this devastating malformation. Copyright © 2012 by the American Society of Nephrology.

U2 - 10.1681/ASN.2012020146

DO - 10.1681/ASN.2012020146

M3 - Article

VL - 23

SP - 1790

EP - 1796

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 11

ER -