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Publication : Tyrosinase Is a Novel Endogenous Regulator of Developmental and Inflammatory Lymphangiogenesis.

First Author  Büttner C Year  2019
Journal  Am J Pathol Volume  189
Issue  2 Pages  440-448
PubMed ID  30448402 Mgi Jnum  J:270508
Mgi Id  MGI:6276436 Doi  10.1016/j.ajpath.2018.10.014
Citation  Buttner C, et al. (2019) Tyrosinase Is a Novel Endogenous Regulator of Developmental and Inflammatory Lymphangiogenesis. Am J Pathol 189(2):440-448
abstractText  Lymphangiogenesis is critically involved in tissue fluid balance, graft rejection, and tumor metastasis. Endogenous regulation of lymphangiogenesis is poorly understood. Herein, we use the lymphatic vessel architecture at the limbal border of the normally avascular cornea, a quantitative trait under strong genetic influence, as a model system to identify new candidate genes regulating lymphangiogenesis. Comparing low-lymphangiogenic BALB/cN with high-lymphangiogenic C57BL/6N mice, we performed quantitative trait loci analysis of five phenotypes in a large BALB/cN x C57BL/6N intercross (n = 795) and identified three to eight genome-wide significant loci, the strongest on chromosome 7 containing tyrosinase (Tyr). Tyrosinase-negative mice showed significantly increased limbal lymph vascularized areas, a higher number of lymphatic vessel end points, and branching points and increased inflammation-induced lymphangiogenesis. These findings confirm that tyrosinase is a novel lymphangiogenesis regulator in developmental and inflammatory lymphangiogenesis. Our findings link melanin synthesis with lymphangiogenesis and open new treatment options in lymphangiogenesis-related diseases.
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