A KO mouse model for the lncRNA Lhx1os produces motor neuron alterations and locomotor impairment
Flaminia Pellegrini,
Vittorio Padovano,
Silvia Biscarini,
Tiziana Santini,
Adriano Setti,
Silvia Giulia Galfrè,
Valentina Silenzi,
Erika Vitiello,
Davide Mariani,
Carmine Nicoletti,
Giulia Torromino,
Elvira De Leonibus,
Julie Martone,
Irene Bozzoni
Affiliations
Flaminia Pellegrini
Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, Italy; Center for Life Nano- & Neuro-Science@Sapienza of Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy
Vittorio Padovano
Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, Italy; Center for Life Nano- & Neuro-Science@Sapienza of Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy
Silvia Biscarini
Center for Life Nano- & Neuro-Science@Sapienza of Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy
Tiziana Santini
Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, Italy; Center for Life Nano- & Neuro-Science@Sapienza of Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy
Adriano Setti
Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, Italy
Silvia Giulia Galfrè
Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, Italy
Valentina Silenzi
Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, Italy; Center for Life Nano- & Neuro-Science@Sapienza of Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy
Erika Vitiello
Center for Human Technologies (CHT) Istituto Italiano di Tecnologia (IIT), 16152 Genova, Italy
Davide Mariani
Center for Human Technologies (CHT) Istituto Italiano di Tecnologia (IIT), 16152 Genova, Italy
Carmine Nicoletti
DAHFMO - Section of Histology and Medical Embryology, Sapienza University of Rome, 00185 Rome, Italy
Giulia Torromino
Institute of Cellular Biology and Neurobiology ''ABT'', CNR, Monterotondo, 00015 Rome, Italy
Elvira De Leonibus
Institute of Cellular Biology and Neurobiology ''ABT'', CNR, Monterotondo, 00015 Rome, Italy; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, 80078 Naples, Italy
Julie Martone
Institute of Molecular Biology and Pathology, CNR, 00185 Rome, Italy; Corresponding author
Irene Bozzoni
Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, Italy; Center for Life Nano- & Neuro-Science@Sapienza of Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy; Center for Human Technologies (CHT) Istituto Italiano di Tecnologia (IIT), 16152 Genova, Italy; Corresponding author
Summary: Here, we describe a conserved motor neuron-specific long non-coding RNA, Lhx1os, whose knockout in mice produces motor impairment and postnatal reduction of mature motor neurons (MNs). The ER stress-response pathway result specifically altered with the downregulation of factors involved in the unfolded protein response (UPR). Lhx1os was found to bind the ER-associated PDIA3 disulfide isomerase and to affect the expression of the same set of genes controlled by this protein, indicating that the two factors act in conjunction to modulate the UPR. Altogether, the observed phenotype and function of Lhx1os indicate its important role in the control of MN homeostasis and function.
