Mutant screen reveals depression-associated Piccolo's control over brain-gonad cross talk and reproductive behavior

Gerardo A. Medrano, Manvendra Singh, Erik J Plautz, Levi B. Good, Karen M. Chapman, Jaideep Chaudhary, Priscilla Jaichander, Heather M. Powell, Ashutosh Pudasaini, John M. Shelton, James A. Richardson, Xian Jin Xie, Zoltán Ivics, Christine Braun, Frauke Ackermann, Craig C. Garner, Zsuzsanna Izsvák, F. Kent Hamra

Research output: Contribution to journalArticlepeer-review

Abstract

Successful sexual reproduction involves complex, genetically encoded interplay between animal physiology and behavior. Here, we report an unbiased forward genetics screen to identify genes that regulate rat reproduction based on mutagenesis via the Sleeping Beauty transposon. As expected, our screen identified genes where reproductive failure was connected to gametogenesis (Btrc, Pan3, Spaca6, Ube2k) and embryogenesis (Alk3, Exoc6b, Slc1a3, Tmx4, Zmynd8). In addition, we identified Atg13 (longevity) and Pclo (neuronal disorders), previously not associated with an inability to conceive. Dominant Pclo traits caused epileptiform activity and affected genes supporting GABAergic synaptic transmission (Gabra6, Gabrg3). Recessive Pclo traits transmitted altered reproductive behavior, including reduced sexual motivation and increased aggression. Pclo mutant behavior was linked to hypothalamic markers for negative energy, compromised brain-gonad crosstalk via disturbed GnRH signaling and allelic markers for major depressive disorder (Grm5, Htr2a, Sorcs3, Negr1, Drd2). Thus, Pclo is a chemosensory-neuroendocrine regulatory factor that calibrates behavioral responses for reproduction.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Aug 31 2018

Keywords

  • Affective disorders
  • Aggression
  • Amygdala
  • Autophagy
  • Conspecific recognition
  • Depression
  • Epilepsy
  • Forward genetics
  • GABAergic
  • Gene-trap
  • Hypothalamus
  • Limbic system
  • Mating
  • Mutagenesis
  • Olfactory
  • Pleiotropy
  • Reproduction
  • Seizures
  • Sleeping Beauty transposon
  • Social behavior
  • Spermatogenesis
  • Spermatogonial

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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