Here, we investigated the differential distribution and genetic determination of ESGs and HFs in the volar skin of C57BL/6 mice and SD rats through gross observation, iodine-starch sweat test, double staining with Nile Blue A and Oil Red O, hematoxylin and eosin (HE) staining, double immunofluorescence staining of LIM Homeobox 2 (LHX2)/Na+-K+-ATPase α1(NKA) or LHX2/Na+-K+-2Cl- cotransporter 1 (NKCC1), and qRT-PCR detection of ESG-related gene Engrailed 1 (En1) and HF-related gene LHX2. The gene discussed is EN1; the disease is hydrops fetalis.