Generation and characterization of Ccdc28b mutant mice links the Bardet-Biedl associated gene with mild social behavioral phenotypes

Abstract

CCDC28B (coiled-coil domain-containing protein 28B) was identified as a modifier in the ciliopathy Bardet-Biedl syndrome (BBS). Our previous work in cells and zebrafish showed that CCDC28B plays a role regulating cilia length in a mechanism that is not completely understood. Here we report the generation of aCcdc28bmutant mouse using CRISPR/Cas9 (Ccdc28b mut). Depletion of CCDC28B resulted in a mild phenotype.Ccdc28b mutanimalsi)do not present clear structural cilia affectation, although we did observe mild defects in cilia density and cilia length in some tissues,ii)reproduce normally, andiii)do not develop retinal degeneration or obesity, two hallmark features of reported BBS murine models. In contrast,Ccdc28b mutmice did show clear social interaction defects as well as stereotypical behaviors. This finding is indeed relevant regardingCCDC28Bas a modifier of BBS since behavioral phenotypes have been documented in BBS. Overall, this work reports a novel mouse model that will be key to continue evaluating genetic interactions in BBS, deciphering the contribution ofCCDC28Bto modulate the presentation of BBS phenotypes. In addition, our data underscores a novel link betweenCCDC28Band behavioral defects, providing a novel opportunity to further our understanding of the genetic, cellular, and molecular basis of these complex phenotypes.