The zebrafish(Danio rerio),with a complete(innate and adaptive)immune system,could be an efficient animal model for immunity and infectious disease because it is convenient to obtain specific mutant zebrafish for elucidation of pathogenicity.Zebrafish has been found to carry two notch1-type genes which are notch 1a and notch 1b,while only Notch1 has been found in mouse and human species.Up to date,the function of notch 1a and notch 1b is not clear,respectively.Here,we report a mutation of notch 1a using the CRISPR/Cas9 system which was deleted 31bp compared with wide type zebrafish.We found the phenotypic changes occurred in the mutative homozygote,only the first 7-9 somite are normally formed,the others are abnormal in 3 days post fertilization(dpf)larva.Moreover,all of the homozygote appear somite curve and will be dead at 10-12 dpf raised in egg water at 28.5 ℃.Then we used Vibrio parahaemolyticus to challenge the 3dpf notch 1a homozygote larva for 2 hours by microinjection of caudal vein,the wide type as a control.The relative expression of qPCR analysis of myD88,mmp9,tnfα,il 1β,cxcl8a are significantly higher than wide type,but the genes of deltaA,deltaB,deltaC,deltaD,dll4,tlr2 and tlr4 have no differentially expressed.In summary,we suggest that mutation of notch 1a gene based on CRISPR/Cas9 system can lead to homozygote larva somite abnormity and finally dead,although the mechanism is unknown.Moreover,the notch 1a gene maybe play an important role to mediate innate immune response to defense Vibrio parahaemolyticus.