A model for gene therapy of human hereditary lymphedema

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Standard

A model for gene therapy of human hereditary lymphedema. / Karkkainen, MJ; Saaristo, A; Jussila, L; Karila, KA; Lawrence, EC; Pajusola, K; Beuler, H; Eichmann, A; Kauppinen, Risto; Kettunen, MI; Yla-Herttuala, S; Finegold, DN; Ferrell, RE; Alitalo, K.

In: National Academy of Sciences. Proceedings, Vol. 98, 23.10.2001, p. 12677-12682.

Research output: Contribution to journalArticle

Harvard

Karkkainen, MJ, Saaristo, A, Jussila, L, Karila, KA, Lawrence, EC, Pajusola, K, Beuler, H, Eichmann, A, Kauppinen, R, Kettunen, MI, Yla-Herttuala, S, Finegold, DN, Ferrell, RE & Alitalo, K 2001, 'A model for gene therapy of human hereditary lymphedema', National Academy of Sciences. Proceedings, vol. 98, pp. 12677-12682. https://doi.org/10.1073/pnas.221449198

APA

Karkkainen, MJ., Saaristo, A., Jussila, L., Karila, KA., Lawrence, EC., Pajusola, K., Beuler, H., Eichmann, A., Kauppinen, R., Kettunen, MI., Yla-Herttuala, S., Finegold, DN., Ferrell, RE., & Alitalo, K. (2001). A model for gene therapy of human hereditary lymphedema. National Academy of Sciences. Proceedings, 98, 12677-12682. https://doi.org/10.1073/pnas.221449198

Vancouver

Karkkainen MJ, Saaristo A, Jussila L, Karila KA, Lawrence EC, Pajusola K et al. A model for gene therapy of human hereditary lymphedema. National Academy of Sciences. Proceedings. 2001 Oct 23;98:12677-12682. https://doi.org/10.1073/pnas.221449198

Author

Karkkainen, MJ ; Saaristo, A ; Jussila, L ; Karila, KA ; Lawrence, EC ; Pajusola, K ; Beuler, H ; Eichmann, A ; Kauppinen, Risto ; Kettunen, MI ; Yla-Herttuala, S ; Finegold, DN ; Ferrell, RE ; Alitalo, K. / A model for gene therapy of human hereditary lymphedema. In: National Academy of Sciences. Proceedings. 2001 ; Vol. 98. pp. 12677-12682.

Bibtex

@article{14c510b59ee042f191a9d31c39c64a62,
title = "A model for gene therapy of human hereditary lymphedema",
abstract = "Primary human lymphedema (Milroy's disease), characterized by a chronic and disfiguring swelling of the extremities, is associated with heterozygous inactivating missense mutations of the gene encoding vascular endothelial growth factor C/D receptor (VEGFR-3). Here, we describe a mouse model and a possible treatment for primary lymphedema. Like the human patients, the lymphedema (Chy) mice have an inactivating Vegfr3 mutation in their germ line, and swelling of the limbs because of hypoplastic cutaneous, but not visceral, lymphatic vessels. Neuropilin (NRP)-2 bound VEGF-C and was expressed in the visceral, but not in the cutaneous, lymphatic endothelia, suggesting that it may participate in the pathogenesis of lymphedema. By using virus-mediated VEGF-C gene therapy, we were able to generate functional lymphatic vessels in the lymphedema mice. Our results suggest that growth factor gene therapy is applicable to human lymphedema and provide a paradigm for other diseases associated with mutant receptors.",
author = "MJ Karkkainen and A Saaristo and L Jussila and KA Karila and EC Lawrence and K Pajusola and H Beuler and A Eichmann and Risto Kauppinen and MI Kettunen and S Yla-Herttuala and DN Finegold and RE Ferrell and K Alitalo",
year = "2001",
month = oct,
day = "23",
doi = "10.1073/pnas.221449198",
language = "English",
volume = "98",
pages = "12677--12682",
journal = "Proceedings of the National Academy of Sciences",
issn = "1091-6490",
publisher = "National Academy of Sciences",

}

RIS

TY - JOUR

T1 - A model for gene therapy of human hereditary lymphedema

AU - Karkkainen, MJ

AU - Saaristo, A

AU - Jussila, L

AU - Karila, KA

AU - Lawrence, EC

AU - Pajusola, K

AU - Beuler, H

AU - Eichmann, A

AU - Kauppinen, Risto

AU - Kettunen, MI

AU - Yla-Herttuala, S

AU - Finegold, DN

AU - Ferrell, RE

AU - Alitalo, K

PY - 2001/10/23

Y1 - 2001/10/23

N2 - Primary human lymphedema (Milroy's disease), characterized by a chronic and disfiguring swelling of the extremities, is associated with heterozygous inactivating missense mutations of the gene encoding vascular endothelial growth factor C/D receptor (VEGFR-3). Here, we describe a mouse model and a possible treatment for primary lymphedema. Like the human patients, the lymphedema (Chy) mice have an inactivating Vegfr3 mutation in their germ line, and swelling of the limbs because of hypoplastic cutaneous, but not visceral, lymphatic vessels. Neuropilin (NRP)-2 bound VEGF-C and was expressed in the visceral, but not in the cutaneous, lymphatic endothelia, suggesting that it may participate in the pathogenesis of lymphedema. By using virus-mediated VEGF-C gene therapy, we were able to generate functional lymphatic vessels in the lymphedema mice. Our results suggest that growth factor gene therapy is applicable to human lymphedema and provide a paradigm for other diseases associated with mutant receptors.

AB - Primary human lymphedema (Milroy's disease), characterized by a chronic and disfiguring swelling of the extremities, is associated with heterozygous inactivating missense mutations of the gene encoding vascular endothelial growth factor C/D receptor (VEGFR-3). Here, we describe a mouse model and a possible treatment for primary lymphedema. Like the human patients, the lymphedema (Chy) mice have an inactivating Vegfr3 mutation in their germ line, and swelling of the limbs because of hypoplastic cutaneous, but not visceral, lymphatic vessels. Neuropilin (NRP)-2 bound VEGF-C and was expressed in the visceral, but not in the cutaneous, lymphatic endothelia, suggesting that it may participate in the pathogenesis of lymphedema. By using virus-mediated VEGF-C gene therapy, we were able to generate functional lymphatic vessels in the lymphedema mice. Our results suggest that growth factor gene therapy is applicable to human lymphedema and provide a paradigm for other diseases associated with mutant receptors.

UR - http://www.scopus.com/inward/record.url?scp=0035940403&partnerID=8YFLogxK

U2 - 10.1073/pnas.221449198

DO - 10.1073/pnas.221449198

M3 - Article

C2 - 11592985

VL - 98

SP - 12677

EP - 12682

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

ER -