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Mutant screen reveals the Piccolo's control over depression and brain-gonad crosstalk

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Item Type:Preprint
Title:Mutant screen reveals the Piccolo's control over depression and brain-gonad crosstalk
Creators Name:Medrano, G.A. and Singh, M. and Plautz, E.J. and Good, L.B. and Chapman, K.M. and Chaudhary, J. and Jaichander, P. and Powell, H.M. and Pudasaini, A. and Shelton, J.M. and Richardson, J.A. and Xie, X.J. and Ivics, Z. and Braun, C. and Ackermann, F. and Garner, C.C. and Izsvak, Z. and Hamra, F.K.
Abstract:Successful sexual reproduction involves a highly complex, genetically encoded interplay between animal physiology and behavior. Here we developed a screen to identify genes essential for rat reproduction based on an unbiased methodology involving 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, our screen identified Atg13 (longevity) Dlg1 and Pclo (neuronal disorders), previously not associated with reproduction. Dominant Pclo traits caused epileptiform activity and affected genes supporting GABAergic synaptic transmission (Gabra6, Gabrg3), and animals exhibited a compromised crosstalk between the brain and gonads via disturbed GnRH signaling. Recessive Pclo traits disrupted conspecific recognition required for courtship/mating and were mapped to allelic markers for major depressive disorder (Grm5, Htr2a, Sorcs3, Negr1, Drd2). Thus, Pclo-deficiency in rats link neural networks controlling sexual motivation to Pclo variants that have been associated with human neurological disorders.
Keywords:Reproduction, Social Behavior, Affective Disorders, Con-Specific Recognition, Mating, Aggression, Depression, Seizures, Epilepsy, GABAergic, Olfactory, Hypothalamus, Amygdala, Forward Genetics, Sleeping Beauty Transposon, Gene-Trap, Mutagenesis, Pleiotropy, Spermatogonial, Spermatogenesis, Acrosome Reaction, Knockout Rat, Autophagy
Source:bioRxiv
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Article Number:405985
Date:31 August 2018
Official Publication:https://doi.org/10.1101/405985

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