Chy3 mice are Vegfc haploinsufficient and exhibit defective dermal superficial to deep lymphatic transition and dermal lymphatic hypoplasia

MT Dellinger, RJ Hunter, MJ Bernas… - … dynamics: an official …, 2007 - Wiley Online Library
MT Dellinger, RJ Hunter, MJ Bernas, MH Witte, RP Erickson
Developmental dynamics: an official publication of the American …, 2007Wiley Online Library
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 …
Abstract
Recent advances in molecular lymphology and lymphatic phenotyping techniques in small animals offer new opportunities to delineate mutant mouse models. Chy3 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 Chy3 mice carry a large chromosomal deletion that includes Vegfc and narrowed this region by monitoring the heterozygosity of genetic markers. We found that Chy3 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 Chy3 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 Chy3 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. Developmental Dynamics 236:2346–2355, 2007. © 2007 Wiley‐Liss, Inc.
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