Universität zu Köln

Buettner, Christian, Clahsen, Thomas, Regenfuss, Birgit, Dreisow, Marie-Luise, Steiber, Zita, Bockt, Felix, Reis, Andre ORCID: 0000-0002-6301-6363 and Cursiefen, Claus (2019). Tyrosinase Is a Novel Endogenous Regulator of Developmental and Inflammatory Lymphangiogenesis. Am. J. Pathol., 189 (2). S. 440 - 449. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1525-2191

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Abstract

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 lymphangiogenesisrelated diseases.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Buettner, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Clahsen, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Regenfuss, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Dreisow, Marie-Luise UNSPECIFIED UNSPECIFIED UNSPECIFIED Steiber, Zita UNSPECIFIED UNSPECIFIED UNSPECIFIED Bockt, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Reis, Andre UNSPECIFIED orcid.org/0000-0002-6301-6363 UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-157727
DOI:	10.1016/j.ajpath.2018.10.014
Journal or Publication Title:	Am. J. Pathol.
Volume:	189
Number:	2
Page Range:	S. 440 - 449
Date:	2019
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1525-2191
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL PROGENITOR CELLS; LYMPHATIC VESSELS; TUMOR LYMPHANGIOGENESIS; ANGIOGENESIS; IDENTIFICATION; MELANOCYTES; METASTASIS; INHIBITOR; MUTATION; CORNEA Multiple languages Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15772