Noon A, Hunter R J, Witte M H, Kriederman B, Bernas M, Rennels M, Percy D, Enerbäck S, Erickson R P
Department of Surgery, University of Arizona, Tucson, USA.
Lymphology. 2006 Jun;39(2):84-94.
FOXC2 mutations cause the lymphatic/ocular disorder Lymphedema-Distichiasis (LD), and Foxc2 haploinsufficient mice mimic this disorder. To determine if FOXC2 overexpression might also cause lymphatic and/or ocular abnormalities, we performed dynamic lymphatic imaging (Evans blue dye), ocular tissue examination, and metabolic profiles in mice: transgenic for FOXC2 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+/-, and Foxc2+/-, Tg but not aP2-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.
FOXC2 突变会导致淋巴管/眼部疾病——先天性淋巴水肿-双行睫（LD），并且 Foxc2 单倍体不足的小鼠可模拟这种疾病。为了确定 FOXC2 的过表达是否也会导致淋巴管和/或眼部异常，我们对小鼠进行了动态淋巴管成像（伊文思蓝染料）、眼部组织检查和代谢分析：与野生型对照（WT）相比，转染了带有脂肪细胞（aP2）启动子的 FOXC2 的转基因小鼠（aP2-FOXC2 Tg）、Foxc2 靶向敲除杂合子（Foxc2+/-）或复合杂合子及转基因小鼠（Foxc2+/-, Tg）。Foxc2+/-; aP2-FOXC2 Tg; 以及 Foxc2+/-, Tg，表现出 LD 独特的淋巴管增生表型，其特征为淋巴管和淋巴结数量增加以及淋巴逆流。Foxc2+/-, 以及 Foxc2+/-, Tg 而非 aP2-FOXC2 Tg 或 WT 表现出异常的眼部表型。此前描述的 aP2-FOXC2 转基因小鼠棕色/白色脂肪分布改变和瘦型表型得到了证实。AP2-FOXC2 Tg 免疫组化显示异位部位，尤其是胚胎心脏中存在异常的 FOXC2 表达。本文还讨论了淋巴系统与脂肪代谢的联系。
