Chy-3 mice are Vegfc haploinsufficient and exhibit defective dermal superficial to deep lymphatic transition and dermal lymphatic hypoplasia

Michael T. Dellinger, Robert J. Hunter, Michael J. Bernas, Marlys H. Witte, Robert P. Erickson

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Recent advances in molecular lymphology and lymphatic phenotyping techniques in small animals offer new opportunities to delineate mutant mouse models. Chy-3 mutant mice were originally named for their chylous ascites, but the underlying lymphatic disorder was not defined. We now re-examined these mice and applied advanced genotyping and lymphatic phenotyping techniques to pinpoint the specific lymphatic defect in this mouse model. We demonstrated that Chy-3 mice carry a large chromosomal deletion that includes Vegfc and narrowed this region by monitoring the heterozygosity of genetic markers. We found that Chy-3 mice not only exhibited chylous ascites but also lymphedema of the hind paws and, in approximately half of the males, lymphedema of the penis. Visual lymphangiography and immunofluorescence staining showed a hypoplastic dermal lymphatic network, whereas the blood vasculature appeared unaffected. This hypoplastic lymphatic network was functional, and all adult Chy-3 mice exhibited a lateral lymphatic pathway directly connecting the inguinal to the axillary lymph node. The dermal superficial to deep lymphatic connections in upper limbs and in all cervical regions were intact and functionally drained the upper body. Lymphatic tracer was not transported from the dermal to the deep truncal lymphatic system in the lower limbs, even though the deep lymphatic vessels and nodes were present and patent. These findings further delineate the lymphatic phenotype of Chy-3 mice, identify a collateral lymph drainage pathway previously undescribed in other genetic models of lymphedema, and demonstrate a predilection for lymphatic abnormalities of the lower limbs.

Original languageEnglish (US)
Pages (from-to)2346-2355
Number of pages10
JournalDevelopmental Dynamics
Volume236
Issue number8
DOIs
StatePublished - Aug 2007

Keywords

  • Chy mice
  • Chy-3 mice
  • Chylous ascites
  • Lymph vasculogenesis
  • Lymphangiogenesis
  • Lymphatic development
  • Lymphatic imaging
  • Lymphatic phenotyping
  • Lymphedema
  • Milroy disease
  • Vegf-c
  • Vegfr-3

ASJC Scopus subject areas

  • Developmental Biology

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