TY - JOUR T1 - Mutant screen reveals depression-associated <em>Piccolo’s</em> control over brain-gonad cross talk and reproductive behavior JF - bioRxiv DO - 10.1101/405985 SP - 405985 AU - Gerardo A. Medrano AU - Manvendra Singh AU - Erik J. Plautz AU - Levi B. Good AU - Karen M. Chapman AU - Jaideep Chaudhary AU - Priscilla Jaichander AU - Heather M. Powell AU - Ashutosh Pudasaini AU - John M. Shelton AU - James A. Richardson AU - Xian-Jin Xie AU - Zoltán Ivics AU - Christine Braun AU - Frauke Ackermann AU - Craig C. Garner AU - Zsuzsanna Izsvák AU - F. Kent Hamra Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/05/14/405985.abstract N2 - 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. ER -