Mouse Anti Chicken PAX7 Hybridoma [QBY8]

Peroxisome Proliferator-Activated Receptor Beta (PPAR beta) is a transcription factor playing an important role in both muscle myogenesis and remodeling, and in inflammation. However, its role in the coordination of the transient muscle inflammation and reparation process following muscle injury has not yet been fully determined. We postulated that activation of the PPAR beta pathway alters the early phase of the muscle regeneration process, i.e. when immune cells infiltrate in injured muscle. Tibialis anteriors of C57BL6/J mice treated or not with the PPAR beta agonist GW0742 were injected with cardiotoxin (or with physiological serum for the contralateral muscle). Muscle regeneration was monitored on days 4, 7, and 14 post-injury. We found that treatment of mice with GW0742 increased, at day 4 post-damage, the recruitment of immune cells (M1 and M2 macrophages) and upregulated the expression of the anti-inflammatory cytokine IL-10 and TGF-beta mRNA. Those effects were accompanied by a significant increase at day 4 of myogenic regulatory factors (Pax7, MyoD, Myf5, Myogenin) mRNA in GW0742-treated mice. However, we showed an earlier return (7 days vs 14 days) of Myf5 and Myogenin to basal levels in GW0742-compared to DMSO-treated mice. Differential effects of GW0742 observed during the regeneration were associated with variations of PPAR beta pathway activity. Collectively, our findings indicate that PPAR beta pathway activity shortens the early phases of skeletal muscle regeneration by increasing the Immune response. (C) 2016 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

PAX binding protein 1 (PAXBP1) is an adaptor protein linking the transcription factor PAX3 and PAX7 to the histone methylation machinery. PAXBP1 is a nuclear protein and its high expression is known in brain cerebellar hemisphere and cerebellum. Moreover, it is also found in abundance in muscle precursor cells that are involved in myogenesis and skeletal muscles formation. Whole genome SNP genotyping and exome sequencing in a family with distinct syndrome of global developmental delay and hypotonia mapped the disease locus to the chromosome 21q22.11 and identified a homozygous missense variant (c.1612C>T) in the PAXBP1 gene, respectively. This variant is predicted to change the highly conserved strongly basic arginine at position 538 in the PAX7 binding domain of PAXBP1 to a neutral cysteine (p.Arg538Cys) residue. Arg538 is highly conserved and the variant is predicted to be deleterious by variety of in silico tools. Furthermore, protein modeling studies showed that in the mutant protein (Cys538), the shorter cysteine is incapable of forming hydrogen bond with the side chain of nearby Asp517 due to its reduced size and lower polarizability. As a consequence, a slight local perturbation of the loop conformation in the PAX7 binding domain of the PAXBP1 protein was observed. Our findings suggest that the pathogenic variant in PAX binding protein underlies distinct syndrome of global developmental delay and myopathic hypotonia. This clinical report should prompt a search for mutations in PAXBP1 in patients presenting with developmental delay and hypotonia. Moreover, these results imply that establishment of PAXBP1 targets and its spatiotemporal interaction will help in understanding of development of cerebellar and will provide basis for developing therapeutic approaches.