| First Author | Au AC | Year | 2010 |
| Journal | Am J Hum Genet | Volume | 87 |
| Issue | 3 | Pages | 436-44 |
| PubMed ID | 20826270 | Mgi Jnum | J:169186 |
| Mgi Id | MGI:4939987 | Doi | 10.1016/j.ajhg.2010.08.008 |
| Citation | Au AC, et al. (2010) Protein tyrosine phosphatase PTPN14 is a regulator of lymphatic function and choanal development in humans. Am J Hum Genet 87(3):436-44 |
| abstractText | The lymphatic vasculature is essential for the recirculation of extracellular fluid, fat absorption, and immune function and as a route of tumor metastasis. The dissection of molecular mechanisms underlying lymphangiogenesis has been accelerated by the identification of tissue-specific lymphatic endothelial markers and the study of congenital lymphedema syndromes. We report the results of genetic analyses of a kindred inheriting a unique autosomal-recessive lymphedema-choanal atresia syndrome. These studies establish linkage of the trait to chromosome 1q32-q41 and identify a loss-of-function mutation in PTPN14, which encodes a nonreceptor tyrosine phosphatase. The causal role of PTPN14 deficiency was confirmed by the generation of a murine Ptpn14 gene trap model that manifested lymphatic hyperplasia with lymphedema. Biochemical studies revealed a potential interaction between PTPN14 and the vascular endothelial growth factor receptor 3 (VEGFR3), a receptor tyrosine kinase essential for lymphangiogenesis. These results suggest a unique and conserved role for PTPN14 in the regulation of lymphatic development in mammals and a nonconserved role in choanal development in humans. |
