Age and sex-dependent ADNP regulation of muscle gene expression is correlated with motor behavior: Possible feedback mechanism with PACAP

Oxana Kapitansky, Shlomo Sragovich, Iman Jaljuli, Adva Hadar, Eliezer Giladi, Illana Gozes

Research output: Contribution to journalArticlepeer-review

Abstract

The activity-dependent neuroprotective protein (ADNP), a double-edged sword, sex-dependently regulates multiple genes and was previously associated with the control of early muscle development and aging. Here we aimed to decipher the involvement of ADNP in versatile muscle gene expression patterns in correlation with motor function throughout life. Using quantitative RT-PCR we showed that Adnp+/− heterozygous deficiency in mice resulted in aberrant gastrocnemius (GC) muscle, tongue and bladder gene expression, which was corrected by the Adnp snippet, drug candidate, NAP (CP201). A significant sexual dichotomy was discovered, coupled to muscle and age-specific gene regulation. As such, Adnp was shown to regulate myosin light chain (Myl) in the gastrocnemius (GC) muscle, the language acquisition gene forkhead box protein P2 (Foxp2) in the tongue and the pituitary-adenylate cyclase activating polypeptide (PACAP) receptor PAC1 mRNA (Adcyap1r1) in the bladder, with PACAP linked to bladder function. A tight age regulation was observed, coupled to an extensive correlation to muscle function (gait analysis), placing ADNP as a muscle-regulating gene/protein.

Original languageEnglish
Article number6715
Pages (from-to)1-15
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume21
Issue number18
DOIs
StatePublished - 2 Sep 2020

Keywords

  • ADNP
  • CatWalk
  • Gene expression
  • Muscle function
  • NAP

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