Skeletal muscle phenotyping of Hippo gene-mutated mice reveals that Lats1 deletion increases the percentage of type I muscle fibers.
Transgenic Res. 31, 227-237 (2022)
The Hippo signal transduction network regulates transcription through Yap/Taz-Tead1-4 in many tissues including skeletal muscle. Whilst transgenic mice have been generated for many Hippo genes, the resultant skeletal muscle phenotypes were not always characterized. Here, we aimed to phenotype the hindlimb muscles of Hippo gene-mutated Lats1−/−, Mst2−/−, Vgll3−/−, and Vgll4+/− mice. This analysis revealed that Lats1−/− mice have 11% more slow type I fibers than age and sex-matched wild-type controls. Moreover, the mRNA expression of slow Myh7 increased by 50%, and the concentration of type I myosin heavy chain is 80% higher in Lats1−/− mice than in age and sex-matched wild-type controls. Second, to find out whether exercise-related stimuli affect Lats1, we stimulated C2C12 myotubes with the hypertrophy agent clenbuterol or the energy stress agent AICAR. We found that both stimulated Lats1 expression by 1.2 and 1.3 fold respectively. Third, we re-analyzed published datasets and found that Lats1 mRNA in muscle is 63% higher in muscular dystrophy, increases by 17–77% after cardiotoxin-induced muscle injury, by 41–71% in muscles during overload-induced hypertrophy, and by 19–21% after endurance exercise when compared to respective controls. To conclude, Lats1 contributes to the regulation of muscle fiber type proportions, and its expression is regulated by physiological and pathological situations in skeletal muscle.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Fiber Type ; Hippo Pathway ; Lats1 ; Skeletal Muscle ; Transgenic mice; Expression; Phosphorylation; Family; Size; Yap
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2022
Prepublished im Jahr
HGF-Berichtsjahr
2022
ISSN (print) / ISBN
0962-8819
e-ISSN
1573-9368
ISBN
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Band: 31,
Heft: 2,
Seiten: 227-237
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Springer
Verlagsort
Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands
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0000-00-00
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Prüfer
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0000-00-00
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0000-00-00
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weitere Inhaber
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Begutachtungsstatus
Peer reviewed
POF Topic(s)
30201 - Metabolic Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-500692-001
G-500600-001
Förderungen
German Center for Diabetes Research (DZD) (MHdA)
German Federal Ministry of Education and Research
Projekt DEAL
Copyright
Erfassungsdatum
2022-05-24