中国生物工程杂志

Astrocyte upregulating gene-1 (AEG-1) is one of found in the brain tissue of HIV patients with dementia. In recent years, studies have shown that AEG-1 regulates a variety of central nervous system diseases, but its study on learning and cognition has not been reported. Hippocampus and cortex play an important role in learning and cognition. In this paper, CRISPR/Cas9 technology combined with Cre/loxp system was used to construct hippocampal cortex specific AEG-1 knockout mice, and the correlation between AEG-1 and learning cognition was preliminarily studied on the basis of this model mouse. Firstly, flox homozygous AEG-1^fl/fl mice inserted into the loxp site were constructed, and bred with hippocampal cortex specific Cre^+/+ recombinase expressing tool mice. Secondly, hippocampal cortex specific AEG-1 knockout mice with AEG-1 ^fl/fl Cre⁺ were selected by PCR. Thirdly,Western blot and immunofluorescence were used to detect the knockout efficiency of AEG-1 gene in the hippocampus and cortex. Last but not least, the new object recognition box and 3-chambered social interaction box combined with SMART 3.0 analysis system were used to preliminarily evaluate the learning memory and social interaction behavior of hippocampal cortico-specific AEG-1 knockout mice. Results: The knockout mice with AEG-1 ^fl/fl Cre⁺ were successfully obtained.AEG-1 protein expression in hippocampus and cortex of mice was significantly lower than that in control group. The new object recognition results showed that the discriminant coefficient of AEG-1 knockout mice was significantly lower than that of the control group, indicating that the learning and memory ability of AEG-1 knockout mice was weak. However, the social interaction showed that there was no significant difference in social interaction between AEG-1 knockout mice and the control group. These results lay the foundation for future studies on AEG-1 in learning cognition.