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

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

Abstract


FOXC2 mutations cause thelymphatic/ocular disorder Lymphedema-Distichiasis (LD), and Foxc2 haploinsufficientmice mimic this disorder. To determine ifFOXC2 overexpression might also causelymphatic and/or ocular abnormalities, weperformed dynamic lymphatic imaging (Evansblue dye), ocular tissue examination, andmetabolic profiles in mice: transgenic forFOXC2 with an adipocyte (aP2) promoter(aP2-FOXC2 Tg), heterozygous for targeteddisruption of Foxc2 (Foxc2+/-), or compoundheterozygous and transgenic (Foxc2+/-, Tg)compared to wild-type controls (WT). Foxc2+/-;aP2-FOXC2 Tg; and Foxc2+/-, Tg, exhibitedLD’s distinctive hyperplastic lymphaticphenotype characterized by increased numberof lymphatic channels and lymph nodes aswell as retrograde lymph reflux. Foxc2+/-, andFoxc2+/-, Tg but not aP2-FOXC2 Tg or WTshowed an abnormal ocular phenotype.Previously described alterations in brown/white fat distribution and lean phenotype inaP2-FOXC2 transgenics were confirmed. AP2-FOXC2 Tg immunohistochemistry disclosedaberrant FOXC2 expression in ectopic sites,especially embryonic heart. Lymphatic systemlinks with fat metabolism are discussed.

Full Text:

PDF