title: Comparative lymphatic, ocular, and metabolic phenotypes of Foxc2 haploinsufficient and aP2-FOXC2 transgenic mice.
abstract: 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.
authors.affiliation: Department of Surgery, University of Arizona, Tucson, USA.
authors.forename: A
authors.initials: A
authors.lastname: Noon
authors.forename: R J
authors.initials: RJ
authors.lastname: Hunter
authors.forename: M H
authors.initials: MH
authors.lastname: Witte
authors.forename: B
authors.initials: B
authors.lastname: Kriederman
authors.forename: M
authors.initials: M
authors.lastname: Bernas
authors.forename: M
authors.initials: M
authors.lastname: Rennels
authors.forename: D
authors.initials: D
authors.lastname: Percy
authors.forename: S
authors.initials: S
authors.lastname: Enerbäck
authors.forename: R P
authors.initials: RP
authors.lastname: Erickson
mesh_terms: D017667:Adipocytes / Q000737:chemistry; D000818:Animals; D004195:Disease Models, Animal; D005140:Eyelashes / Q000002:abnormalities*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000378:metabolism; D044148:Lymphatic Abnormalities / Q000235:genetics / Q000473:pathology; D008209:Lymphedema / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
chemical_list: D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D051858:Forkhead Transcription Factors; D007328:Insulin; C082078:mesenchyme fork head 1 protein; D005947:Glucose