Attractin Gene Deficiency in Rats Leads to Impairments in Both Activity and Spatial Learning and Memory

Attractin (ATRN), an autosomal recessive gene that is widely distributed in the brain, is involved in the execution of a variety of brain functions and associated with certain neuropsychiatric disorders. Here, we intro-duce a novel rat strain harboring a mutation in ATRN that was generated by knocking in ATRN-G505C via the CRISPR/Cas9 system. We assessed the behavioral performance of these mutant ATRN knock-in rats. The G505C mutation was introduced into exon 9, and a synthetic primer was inserted into introns 8-9 for genotyping. The 505th amino acid, a Gly (G) residue, was mutated to a Cys (C) residue, i.e., GGC was mutated to TGC. Behav-ioral experiments showed that homozygous ATRN rats spent significantly more time searching for the escape platform in the acquisition trial and significantly less time in the target area in the probe trial in the Morris water maze (MWM) test and traveled a significantly shorter distance in the open field test (OFT) than wild-type rats. In addition, Western blot analysis and immunohistochemistry showed that rats with the mutant ATRN gene exhib-ited significantly reduced expression of brain-derived neurotrophic factor (BDNF). In summary, our results indi-cate that mutations in the ATRN gene directly lead to learning and memory impairments and slight motor deficits. These findings provide new clues for the mechanism by which mutant ATRN induces neurodegenerative changes. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

The introduction of a novel rat strain with a mutation in the ATRN gene reveals learning and memory impairments, as well as slight motor deficits and behavioral abnormalities in these mutant rats. These findings provide new insights into the mechanisms by which mutant ATRN induces neurodegenerative changes.