Given the prior findings with transgenic KATP GOF animals, and the prominence of Kir6.1 and SUR2 in lymphatic smooth muscle, we sought to understand the extent to which lymphatic contractile function might be compromised in mice with CS-associated mutations, with the potential to explain the susceptibility of CS patients to lymphedema, using both ex vivo and in vivo assays in heterozygous Kir6.1[V65M], hetero- and homozygous SUR2[A478V] mice and, for completeness, in homozygous SUR2[R1154Q] mice. This evidence concerns the gene KCNJ8 and lymphedema.