Nuclear factor-κB (NF-κB) regulates multiple aspects of innate and adaptive immune functions and acts as key mediators of inflammatory responses. Bcl3 is a member of the inhibitor of the NF-κB (IκB) family and functions as a co-factor of the p52 homodimer. NF-κB2/p100 (precursor of p52) and Bcl3 have functionally redundant roles in preventing the immune system from attacking its host. However, it is not clear in which aspects they have redundant functions or cooperate with each other. We used zebrafish as a research model to generate mutant fish nfkb2-/-, bcl3-/-, and nfkb2-/-/bcl3-/-.

Reduced expression of immune cell marker genes, absence of Hassall's corpuscles in the thymus, nuclear displacement and pyknotic of hepatocytes were observed in nfkb2-/- and bcl3-/-zebrafish. These results demonstrate that knockout of nfkb2 and bcl3 impairs zebrafish immunity. bcl3-/- zebrafish grow slowly and are smaller in size. We found that the expression of growth factors was decreased in bcl3-/- zebrafish, and the exercise ability and food intake were decreased. We hypothesize that Bcl3 participates in the growth and development regulated by GH/IGF signaling pathway through NF-κB signaling pathway, or is involved in GH/IGF signaling pathway independently. NF-κB2/p100 and Bcl3 play different roles in fin regeneration. The nfkb2-/- zebrafish promote fin regeneration, while bcl3-/- zebrafish reduce fin regeneration.

This project investigates the roles of NF-κB2/p100 and Bcl3 in zebrafish growth, fin regeneration and immunity.