Gobiocypris rarus
is sensitive to environmental pollution, especially to heavy metal and grass carp reovirus (GCRV). Hence, it has potential utility as a biological monitor. Genetic deciphering of its unique immune system will advance our understanding of its unique adaptive strategies, which provide cues for its better application. A de novo genome of rare minnow was obtained, and its sex determination mechanism is ZZ/ZW. We identified several specific mutation genes and specific lost genes of rare minnow, and these might be related to the sensitivity of rare minnow to environmental stimuli. We also analyzed the gene expression level of different organs/tissues and found that several
IFIT
genes may play key roles in GCRV resistance. In addition, knockout of the gene
PCDH10L
indicates that
PCDH10L
affects Pb
2+
-induced mortality in rare minnow. Rare minnow is ready for genetic manipulation and shows potential as an emerging experimental model.