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The research protocol and all animal care procedures were approved by the Institutional Animal Care and Use Committee (IACUC protocol #2302) at Cedars-Sinai Medical Center. The following congenic mouse strains were used: Endothelin Receptor B-null Ednrb^tm1Ywa/J on 129SvIm/J background and Ednrb^tm1Ywa/J on C57/B6J background originally imported from Jackson Laboratory (Bar Harbor, ME, USA) this strain is available at The Jackson Laboratory Repository with the JAX Stock No. 021933; Endothelin 3-null Edn3^tm1Ywa/J on 129SvEv background were a gift of Masashi Yanagisawa, University of Texas Southwestern Medical Center at Dallas. The breeding scheme, animal care and genotyping were performed as previously described [13 (link)]. The homozygotes (we refer to these as Ednrb^−/− and Edn3^−/− in this paper) are easily identified by the white coat color and progressively enlarging abdomens due to aganglionosis leading to megacolon. The wild-type and heterozygote littermates (we refer to these as Ednrb^+/+ and Ednrb+/−, Edn3+/+ and Edn3+/−, respectively), are phenotypically normal. All studies were performed with congenic 129Sv Edn3 and Ednrb mice, except for bone marrow transplant studies that were performed with congenic B6 Ednrb mice. RAG2-null mice (RAG2^−/−) (B6.SJL (129S6)-Ptprc^a/BoyCrTac-Rag2^tm1Fwa N10) were purchased from Taconic.