Articles

COMPARATIVE LYMPHATIC, OCULAR, AND METABOLIC PHENOTYPES OF FOXC2 HAPLOINSUFFICIENT AND AP2-FOXC2 TRANSGENIC MICE

Authors
  • A Noon
  • RJ Hunter
  • MH Witte
  • B Kriederman
  • MJ Bernas
  • M Rennels
  • D Percy
  • S Enerback
  • RP Erickson

Abstract

FOXC2 mutations cause the lymphatic/ocular disorder Lymphedema-Distichiasis (LD), and Foxc2 haploinsufficient mice mimic this disorder. To determine ifFOXC2 overexpression might also cause lymphatic and/or ocular abnormalities, we performed dynamic lymphatic imaging (Evansblue dye), ocular tissue examination, and metabolic profiles in mice: transgenic forFOXC2 with an adipocyte (aP2) promoter (aP2-FOXC2 Tg), heterozygous for targeted disruption of Foxc2 (Foxc2+/-), or compound heterozygous and transgenic (Foxc2+/-, Tg) compared to wild-type controls (WT). Foxc2+/-; aP2-FOXC2 Tg; and Foxc2+/-, Tg, exhibited LD's distinctive hyperplastic lymphatic phenotype characterized by increased number of lymphatic channels and lymph nodes as well as retrograde lymph reflux. Foxc2+/-, andFoxc2+/-, Tg but not a P2-FOXC2 Tg or WT showed an abnormal ocular phenotype. Previously described alterations in brown/white fat distribution and lean phenotype in aP2-FOXC2 transgenics were confirmed. AP2-FOXC2 Tg immunohistochemistry disclosed aberrant FOXC2 expression in ectopic sites,especially embryonic heart. Lymphatic system links with fat metabolism are discussed.

Keywords: FOXC2, Foxc2, lymphatic hyperplasia, haploinsufficient, transgenic, Lymphedema-Distichiasis, ocular, adipocyte

How to Cite:

Noon, A. & Hunter, R. & Witte, M. & Kriederman, B. & Bernas, M. & Rennels, M. & Percy, D. & Enerback, S. & Erickson, R., (2006) “COMPARATIVE LYMPHATIC, OCULAR, AND METABOLIC PHENOTYPES OF FOXC2 HAPLOINSUFFICIENT AND AP2-FOXC2 TRANSGENIC MICE”, Lymphology 39(2), p.84-94.

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Published on
21 Aug 2006
Peer Reviewed