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. 2023 Dec 18;33(4):12174.
doi: 10.4081/ejtm.2023.12174.

Pax7 reporter mouse models: a pocket guide for satellite cell research

Huascar Pedro Ortuste Quiroga  1 , Shin Fujimaki  2 , Yusuke Ono  3
Affiliations

Pax7 reporter mouse models: a pocket guide for satellite cell research

Huascar Pedro Ortuste Quiroga et al. Eur J Transl Myol. .

Abstract

Since their discovery, satellite cells have showcased their need as primary contributors to skeletal muscle maintenance and repair. Satellite cells lay dormant, but when needed, activate, differentiate, fuse to fibres and self-renew, that has bestowed satellite cells with the title of muscle stem cells. The satellite cell specific transcription factor Pax7 has enabled researchers to develop animal models against the Pax7 locus in order to isolate and characterise satellite cell-mediated events. This review focuses specifically on describing Pax7 reporter mouse models. Here we describe how each model was generated and the key findings obtained. The strengths and limitations of each model are also discussed. The aim is to provide new and current satellite cell enthusiasts with a basic understanding of the available Pax7 reporter mice and hopefully guide selection of the most appropriate Pax7 model to answer a specific research question.

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Conflict of interest statement

We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Human body contains more than 700 skeletal muscles, which account for up to ~40% of the total body mass in men and ~30% in females. Skeletal muscle is comprised of highly specialised multinucleated myofibres formed during embryonic and foetal development. Each myofibre contains hundreds of myofibrils which themselves consist of thousands of sarcomeres that contain the actin and myosin filaments that interact to produce force. The peripherally located myonuclei on myofibres are post-mitotic, thus as muscle precursors (myoblasts) enter terminal differentiation and fuse, the contributed nuclei lose the ability to re-enter the cell cycle. Therefore, in order to supply new myonuclei for growth, maintenance and repair, skeletal muscle relies on a population of mononuclear stem cells, adequately termed satellite cells, due to their location on the plasmalemma of a muscle fibre within the ensheathing basal lamina. Mammalian adult skeletal muscle has a relatively slow turnover of myonuclei; hence satellite cells are mitotically quiescent. However, in response to physiological stimuli (damage, resistive exercise and disease), satellite cells are rapidly activated, providing highly proliferative myoblasts which then enter myogenic differentiation and fuse to damaged muscle fibres or form new fibres de novo. In order to preserve a pool of mitotically quiescent stem cells for future regenerative bouts, satellite cells undergo self-renewal. It is impossible to mention satellite cells without mentioning the transcription factor paired-box 7 (Pax7). A member of the paired box containing family of transcription factors, Pax7 is expressed in quiescent and activated satellite cells. Although other cell surface markers and their expression levels (e.g. CD34, CD29, CXCR4, c-met, M-cad) can be used to identify satellite cells, the consensus remains that the presence of Pax7 in adult mammalian muscle best identifies all satellite cells with myogenic potential. Indeed, co-labelling of Pax7 with myogenic regulatory factors such as MyoD and Myogenin can help differentiate distinct aspects of the myogenic program. For example activated satellite cells express both MyoD and Pax7, whereas cells entering the differentiation phase express Myogenin but not Pax7. In addition, co-immunolabelling of Pax7 with the membrane protein laminin, enables visualisation of satellite cells and the underneath myofibre they are in contact with.

Although there is some debate regarding the exact role of satellite cells in adult muscle regeneration, it is without doubt that the presence of satellite cells in regenerating muscle is indispensable. Indeed, selective ablation of Pax7 positive satellite cells results in significant loss of muscle recovery post injury. Furthermore, Pax7 null mice are not viable beyond 3 weeks of birth, with surviving mice being significantly smaller in size and weight., With such an integral role, it is understandable that efforts to generate animal models focus on manipulation of the Pax7 gene in order to recapitulate satellite cell governed events. The mouse is the main go-to model for the development of transgenic models. In fact, mice are most frequently used to model main aspects of muscular dystrophies., Unsurprisingly, mice comprise the majority of the current Pax7 reporter animal models. However, due to underlying complex dynamics of satellite cell regulation, choosing which Pax7 mouse model to use is key to facilitate the correct interpretation of data and understand satellite cell biology.

In this review we will introduce the currently available Pax7 reporter mice. We will highlight, using examples from key studies, how these models were developed, the main results obtained, as well as their advantages and disadvantages. The main characteristics of these models are summarised and collated in a table (Supplementary Table 1). The aim of this review is to provide a concise background and comparison of the available Pax7 reporter mice. Hopefully this will aid selection of the most appropriate model(s) to answer key questions regarding satellite cell-governed events.

Figures

Fig 1.
Fig 1.
Simplified schematic representing the modification of the Pax7 locus on the different reporter mice models. A) Pax7-ZsGreen, B) Pax7-nGFP, C) Pax7-EGFP and D) Pax7-YFP. E : exon Neo : Neomycin
Fig 2.
Fig 2.
Simplified schematic representing the modification of the Pax7 locus on the different inducible mice models. A) Pax7CE and B) Pax7CreERT2. E : exon IRES : Internal Ribosomal Entry Site.
See this image and copyright information in PMC

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