Impact of miR-29c Overexpression on Skeletal Muscle Mass and Function in Mice

• Grant number: 25/12456-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2025
• End date: July 31, 2027
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Anselmo Sigari Moriscot
• Grantee: Luis Antonio Chinait Hess Costa Dutra
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 25/00791-5 - Impact of miR29c overexpression on skeletal muscle mass and function in mice, AP.R

Abstract

The scholarship recipient will receive the animals built by Jackson Lab, B6.Cg-Tg(ACTA1-cre/ERT2) 97.16Mtz/JJackson Lab, cat# JAX:039097 and also the custom loxP-NeoSTOP-miR-29c mice.It will promote the development of the colony of CRE-driver animals (B6.Cg-Tg(ACTA1-cre/ERT2) 97.16Mtz/J) and loxP animals (loxP-NeoSTOP-miR-29c), monitoring the profile throughgenotyping to measure the passing of the machinery to the next generations of the colony. Thesubject will make dosage response curves from the use of tamoxifen for muscle Cre production withthe minimum dose and maximum production. It will carry out the index between the two colonies for the construction ofa new colony "ACTA1-cre/loxP-NeoSTOP-miR-29c", which will also undergo precisiongenotyping process.The fellow will then characterize the miR-29c expression response afterinduction with tamoxifen. Will evaluate the expression of miR-29c through pcr in the tibialis musclesanterior, soleus, diaphragm, masseter, erector spinae and heart over time, using 7, 14,28 and 56 days as a basis. In addition to the muscles, he will also perform histological analyzes on the organsheart, kidney and liver. It will measure the cross-sectional area of ¿¿the skeletal muscles describedabove, by type of muscle fiber (I, IIa, IIb and IIx), in addition, functional analyzes will be carried out to measurethe change in maximum tetanic force of the soleus and anterior tibialis muscles. Just as, alsowill measure the level of intracellular activity of pathways of interest, responsible for mass gainmuscle mass such as RAS-MEK-ERK, p38 and muscle mass loss pathways such asubiquitin-proteasome (Atrogin-1 and MuRF). The scholarship holder will also deepen the analysis of the transcriptome of the tibialis anterior muscleoverexpressing miR29c obtained in a previous project. Develop quality checks andalignment, as well as differential expression analyses. Will perform enrichment analysisusing GO and KEGG. It will also perform protein-protein interaction analyzes and generate interaction networksmRNA - microRNA of interest to the transcriptome. (AU)