The DOI matches its Crossref record.
A model for gene therapy of human hereditary lymphedema
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease
Da Mesquita, S., Louveau, A., Vaccari, A., Smirnov, I., Cornelison, R. C., Kingsmore, K. M., Contarino, C., Onengut-Gumuscu, S., Farber, E., Raper, D., et al. (2018) · Nature · doi:10.1038/s41586-018-0368-8 · Cited by 1,445
Petrova, T. V., Mäkinen, T., Mäkelä, T. P., Saarela, J., Virtanen, I., Ferrell, R. E., Finegold, D. N., Kerjaschki, D., Ylä‐Herttuala, S., & Alitalo, K. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf470 · Cited by 632
Self-citationAbnormal lymphatic vessel development in neuropilin 2 mutant mice
Yuan, L., Moyon, D., Pardanaud, L., Bréant, C., Karkkainen, M. J., Alitalo, K., & Eichmann, A. (2002) · Development · doi:10.1242/dev.129.20.4797 · Cited by 632
Self-citationLymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity
Harvey, N. L., Srinivasan, R. S., Dillard, M. E., Johnson, N. C., Witte, M. H., Boyd, K., Sleeman, M. W., & Oliver, G. (2005) · Nature Genetics · doi:10.1038/ng1642 · Cited by 580
Integrin-α9 Is Required for Fibronectin Matrix Assembly during Lymphatic Valve Morphogenesis
Bazigou, E., Xie, S., Chen, C., Weston, A., Miura, N., Sorokin, L., Adams, R., Muro, A. F., Sheppard, D., & Makinen, T. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.06.017 · Cited by 347
Metadata
- Authors
- Karkkainen, M. J., Saaristo, A., Jussila, L., Karila, K. A., Lawrence, E. C., Pajusola, K., Bueler, H., Eichmann, A., Kauppinen, R., Kettunen, M. I., Ylä-Herttuala, S., Finegold, D. N., Ferrell, R. E., & Alitalo, K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-10-09
- Volume
- 98
- Issue
- 22
- Pages
- 12677-12682
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2128418259
- Cited by
- 606
- References
- 0
- FWCI
- 12.75
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: A model for gene therapy of human hereditary lymphedema. https://app.cochat.ai/papers/10.1073/pnas.221449198
- The paper
- Karkkainen, M. J., Saaristo, A., Jussila, L., Karila, K. A., Lawrence, E. C., Pajusola, K., Bueler, H., Eichmann, A., Kauppinen, R., Kettunen, M. I., Ylä-Herttuala, S., Finegold, D. N., Ferrell, R. E., & Alitalo, K. (2001). A model for gene therapy of human hereditary lymphedema. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.221449198
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
