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Review
. 2022 Mar 29:16:876304.
doi: 10.3389/fncir.2022.876304. eCollection 2022.

P2X7 Receptor-Related Genetic Mouse Models - Tools for Translational Research in Psychiatry

Lidia Urbina-Treviño  1   2 , Iven-Alex von Mücke-Heim  1   3 , Jan M Deussing  1
Affiliations
Review

P2X7 Receptor-Related Genetic Mouse Models - Tools for Translational Research in Psychiatry

Lidia Urbina-Treviño et al. Front Neural Circuits. .

Abstract

Depression is a common psychiatric disorder and the leading cause of disability worldwide. Although treatments are available, only about 60% of treated patients experience a significant improvement in disease symptoms. Numerous clinical and rodent studies have identified the purinergic P2X7 receptor (P2X7R) as one of the genetic factors potentially contributing to the disease risk. In this respect, genetically engineered mouse models targeting the P2X7R have become increasingly important in studying designated immunological features and subtypes of depression in vivo. This review provides an overview of the P2X7R -related mouse lines currently available for translational psychiatric research and discusses their strengths, weaknesses, and potentials.

Keywords: P2X7 receptor; depression; genetic mouse model; purinergic signaling; translational psychiatry.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Strategies targeting the P2RX7 gene in constitutive and conditional knockout mouse lines. (A) P2X7R constitutive knockout alleles. GSK (P2rx7tm1Ipch): a LacZ-neomycin (neo) cassette was inserted in exon 1, which results in an exon 1-LacZ fusion transcript. Lexicon Genetics (P2rx7tm1Lex): a LacZ-neomycin cassette was used to substitute exons 2 and 3, which results in an exon 1-LacZ-neo fusion transcript. Pfizer (P2rx7tm1Gab): a neomycin cassette was inserted in exon 13, which truncates the transcript in the C-terminal region. “*”: truncated P2X7R exon. Dashed lines indicated the insertion site of the construct. (B) Humanized P2X7R locus. The human cDNA sequence from exon 2–13 substitute’s murine exon 2. The cDNA sequence is flanked by LoxP sites. (C) P2X7R conditional knockout locus. Upon Cre recombinase activity, the cDNA fragment is deleted resulting in a disrupted P2RX7 gene. The loss of exon 2 prevents the expression of any functional P2X7R variants. “pA/red box”: Polyadenylation signal.
FIGURE 2
FIGURE 2
Constructs used for generation of BAC transgenic reporter mice. (A) P2X7R -EGFP: An EGFP cassette was inserted downstream of the P2X7R coding sequence in exon 13 creating a P2X7R -EGFP fusion transcript. (B) sEGFP: An EGFP cassette was inserted at the ATG of the P2X7R in exon 1, theoretically blocking the transcription of the remainder of the gene through its poly A signal. The P2rx4 gene is present 16 kb downstream of the P2X7R construct. “pA/red box”: Polyadenylation signal.
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