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Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin

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Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin. / Huber, Tobias B; Kwoh, Christopher; Wu, Hui; Asanuma, Katsuhiko; Gödel, Markus; Hartleben, Björn; Blumer, Ken J; Miner, Jeffrey H; Mundel, Peter; Shaw, Andrey S.

In: J CLIN INVEST, Vol. 116, No. 5, 05.2006, p. 1337-45.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Huber, TB, Kwoh, C, Wu, H, Asanuma, K, Gödel, M, Hartleben, B, Blumer, KJ, Miner, JH, Mundel, P & Shaw, AS 2006, 'Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin', J CLIN INVEST, vol. 116, no. 5, pp. 1337-45. https://doi.org/10.1172/JCI27400

APA

Huber, T. B., Kwoh, C., Wu, H., Asanuma, K., Gödel, M., Hartleben, B., Blumer, K. J., Miner, J. H., Mundel, P., & Shaw, A. S. (2006). Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin. J CLIN INVEST, 116(5), 1337-45. https://doi.org/10.1172/JCI27400

Vancouver

Huber TB, Kwoh C, Wu H, Asanuma K, Gödel M, Hartleben B et al. Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin. J CLIN INVEST. 2006 May;116(5):1337-45. https://doi.org/10.1172/JCI27400

Bibtex

@article{45122389bdab4a9c940e0ba79611950a,
title = "Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin",
abstract = "Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular diagnosis resulting in end-stage renal disease. Defects in several podocyte proteins have been implicated in the etiology of FSGS, including podocin, alpha-actinin-4, CD2-associated protein (CD2AP), and TRPC6. Despite our growing understanding of genes involved in the pathogenesis of focal segmental sclerosis, the vast majority of patients with this disease, even those with a familial linkage, lack a clear genetic diagnosis. Here, we tested whether combinations of genetic heterozygosity (bigenic heterozygosity) that alone do not result in clinical kidney disease could function together to enhance susceptibility to glomerular damage and FSGS. Combinations of Cd2ap heterozygosity and heterozygosity of either synaptopodin (Synpo) or Fyn proto-oncogene (Fyn) but not kin of IRRE like 1 (Neph1) resulted in spontaneous proteinuria and in FSGS-like glomerular damage. These genetic interactions were also reflected at a functional level, as we found that CD2AP associates with Fyn and Synpo but not with Neph1. This demonstrates that bigenic heterozygosity can lead to FSGS and suggests that combined mutations in 2 or multiple podocyte genes may be a common etiology for glomerular disease.",
keywords = "Adaptor Proteins, Signal Transducing, Animals, Cell Line, Cytoskeletal Proteins, Disease Models, Animal, Genetic Predisposition to Disease, Glomerulosclerosis, Focal Segmental, Heterozygote, Humans, Kidney Failure, Chronic, Mice, Mice, Transgenic, Microfilament Proteins, Mutation, Proteins, Proto-Oncogene Proteins c-fyn, Journal Article, Research Support, Non-U.S. Gov't",
author = "Huber, {Tobias B} and Christopher Kwoh and Hui Wu and Katsuhiko Asanuma and Markus G{\"o}del and Bj{\"o}rn Hartleben and Blumer, {Ken J} and Miner, {Jeffrey H} and Peter Mundel and Shaw, {Andrey S}",
year = "2006",
month = may,
doi = "10.1172/JCI27400",
language = "English",
volume = "116",
pages = "1337--45",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "5",

}

RIS

TY - JOUR

T1 - Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin

AU - Huber, Tobias B

AU - Kwoh, Christopher

AU - Wu, Hui

AU - Asanuma, Katsuhiko

AU - Gödel, Markus

AU - Hartleben, Björn

AU - Blumer, Ken J

AU - Miner, Jeffrey H

AU - Mundel, Peter

AU - Shaw, Andrey S

PY - 2006/5

Y1 - 2006/5

N2 - Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular diagnosis resulting in end-stage renal disease. Defects in several podocyte proteins have been implicated in the etiology of FSGS, including podocin, alpha-actinin-4, CD2-associated protein (CD2AP), and TRPC6. Despite our growing understanding of genes involved in the pathogenesis of focal segmental sclerosis, the vast majority of patients with this disease, even those with a familial linkage, lack a clear genetic diagnosis. Here, we tested whether combinations of genetic heterozygosity (bigenic heterozygosity) that alone do not result in clinical kidney disease could function together to enhance susceptibility to glomerular damage and FSGS. Combinations of Cd2ap heterozygosity and heterozygosity of either synaptopodin (Synpo) or Fyn proto-oncogene (Fyn) but not kin of IRRE like 1 (Neph1) resulted in spontaneous proteinuria and in FSGS-like glomerular damage. These genetic interactions were also reflected at a functional level, as we found that CD2AP associates with Fyn and Synpo but not with Neph1. This demonstrates that bigenic heterozygosity can lead to FSGS and suggests that combined mutations in 2 or multiple podocyte genes may be a common etiology for glomerular disease.

AB - Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular diagnosis resulting in end-stage renal disease. Defects in several podocyte proteins have been implicated in the etiology of FSGS, including podocin, alpha-actinin-4, CD2-associated protein (CD2AP), and TRPC6. Despite our growing understanding of genes involved in the pathogenesis of focal segmental sclerosis, the vast majority of patients with this disease, even those with a familial linkage, lack a clear genetic diagnosis. Here, we tested whether combinations of genetic heterozygosity (bigenic heterozygosity) that alone do not result in clinical kidney disease could function together to enhance susceptibility to glomerular damage and FSGS. Combinations of Cd2ap heterozygosity and heterozygosity of either synaptopodin (Synpo) or Fyn proto-oncogene (Fyn) but not kin of IRRE like 1 (Neph1) resulted in spontaneous proteinuria and in FSGS-like glomerular damage. These genetic interactions were also reflected at a functional level, as we found that CD2AP associates with Fyn and Synpo but not with Neph1. This demonstrates that bigenic heterozygosity can lead to FSGS and suggests that combined mutations in 2 or multiple podocyte genes may be a common etiology for glomerular disease.

KW - Adaptor Proteins, Signal Transducing

KW - Animals

KW - Cell Line

KW - Cytoskeletal Proteins

KW - Disease Models, Animal

KW - Genetic Predisposition to Disease

KW - Glomerulosclerosis, Focal Segmental

KW - Heterozygote

KW - Humans

KW - Kidney Failure, Chronic

KW - Mice

KW - Mice, Transgenic

KW - Microfilament Proteins

KW - Mutation

KW - Proteins

KW - Proto-Oncogene Proteins c-fyn

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1172/JCI27400

DO - 10.1172/JCI27400

M3 - SCORING: Journal article

C2 - 16628251

VL - 116

SP - 1337

EP - 1345

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 5

ER -