Piezo2-KO Mouse

Piezo2, also known as Fam38B, is a vertebrate multipass transmembrane protein and an essential component of mechanically activated cation channels [1]. Mechanosensation, which Piezo2 is involved in, is crucial for numerous physiological processes such as touch, proprioception, and bladder stretch sensation [2,3].

In KO mouse models, Piezo2-deficient proprioceptive neurons led to severely uncoordinated body movements and abnormal limb positions, indicating that Piezo2 is the major mechanotransducer of mammalian proprioceptors [4]. In Merkel-cell-specific Piezo2-deficient mice, Merkel-cell mechanosensitivity was completely lost, and in vivo slowly adapting responses mediated by the Merkel cell-neurite complex had reduced static firing rates [7]. Nociceptor-specific Piezo2 conditional knockout mice were protected from mechanical sensitization associated with inflammatory joint pain and osteoarthritis [6]. In humans, loss-of-function mutations in PIEZO2 result in an autosomal recessive syndrome of muscular atrophy with perinatal respiratory distress, arthrogryposis, and scoliosis [5].

In conclusion, Piezo2 is vital for mechanosensation in various physiological processes. Studies using KO and CKO mouse models have revealed its role in proprioception, Merkel-cell mechanotransduction, and mechanical sensitization in diseases like osteoarthritis. Understanding Piezo2 through these research models provides insights into the molecular mechanisms of mechanosensation and potential therapeutic targets for related diseases.

References:

1. Coste, Bertrand, Mathur, Jayanti, Schmidt, Manuela, Dubin, Adrienne E, Patapoutian, Ardem. 2010. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. In Science (New York, N.Y.), 330, 55-60. doi:10.1126/science.1193270. https://pubmed.ncbi.nlm.nih.gov/20813920/

2. Szczot, Marcin, Nickolls, Alec R, Lam, Ruby M, Chesler, Alexander T. . The Form and Function of PIEZO2. In Annual review of biochemistry, 90, 507-534. doi:10.1146/annurev-biochem-081720-023244. https://pubmed.ncbi.nlm.nih.gov/34153212/

3. Villarino, Nicholas W, Hamed, Yasmeen M F, Ghosh, Britya, Patapoutian, Ardem, Marshall, Kara L. 2023. Labeling PIEZO2 activity in the peripheral nervous system. In Neuron, 111, 2488-2501.e8. doi:10.1016/j.neuron.2023.05.015. https://pubmed.ncbi.nlm.nih.gov/37321223/

4. Woo, Seung-Hyun, Lukacs, Viktor, de Nooij, Joriene C, Wilkinson, Katherine A, Patapoutian, Ardem. 2015. Piezo2 is the principal mechanotransduction channel for proprioception. In Nature neuroscience, 18, 1756-62. doi:10.1038/nn.4162. https://pubmed.ncbi.nlm.nih.gov/26551544/

5. Alper, S L. 2017. Genetic Diseases of PIEZO1 and PIEZO2 Dysfunction. In Current topics in membranes, 79, 97-134. doi:10.1016/bs.ctm.2017.01.001. https://pubmed.ncbi.nlm.nih.gov/28728825/

6. Obeidat, Alia M, Wood, Matthew J, Adamczyk, Natalie S, Malfait, Anne-Marie, Miller, Rachel E. 2023. Piezo2 expressing nociceptors mediate mechanical sensitization in experimental osteoarthritis. In Nature communications, 14, 2479. doi:10.1038/s41467-023-38241-x. https://pubmed.ncbi.nlm.nih.gov/37120427/

7. Woo, Seung-Hyun, Ranade, Sanjeev, Weyer, Andy D, Stucky, Cheryl L, Patapoutian, Ardem. 2014. Piezo2 is required for Merkel-cell mechanotransduction. In Nature, 509, 622-6. doi:10.1038/nature13251. https://pubmed.ncbi.nlm.nih.gov/24717433/