Mutation of the attractin gene impairs working memory in rats

OBJECTIVE: Attractin (ATRN) is a widely expressed member of the cell adhesion and guidance protein family in humans that is closely related to cellular immunity and neurodevelopment. However, while previous studies in our laboratory have confirmed the effect of ATRN mutations on long‐term memory, its specific role and the molecular mechanism by which it influences spatial cognition are poorly understood. METHODS: This study aimed to examine the effect of ATRN mutations on working memory in water maze with a novel ATRN‐mutant rat generated by the CRISPR/Cas9 system; the mutation involved the substitution of the 505th amino acid, glycine (G), with cysteine (C), namely, a mutation from GGC to TGC. The changes in myelin basic protein (MBP) expression in rats were also analyzed with the western blot. RESULTS: The ATRN‐G505C(KI/KI) rats exhibited significant increases in the required latency and distance traveled to locate the escape platform in a Morris water maze test of working memory. In addition, the expression of MBP was reduced in ATRN‐mutant rats, as shown in the western blot analysis. CONCLUSION: Our results indicate that ATRN gene mutations may directly lead to the impairment of working memory in the water maze; this impairment may be due to the inhibition of MBP expression, which in turn affects the spatial cognition.