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

doi:10.1016/j.isci.2022.105891

A KO mouse model for the lncRNA Lhx1os produces motor neuron alterations and locomotor impairment

iScience. 2022 Dec 28;26(1):105891. doi: 10.1016/j.isci.2022.105891. eCollection 2023 Jan 20.

Authors

Flaminia Pellegrini^{1

2}, Vittorio Padovano^{1

2}, Silvia Biscarini², Tiziana Santini^{1

2}, Adriano Setti¹, Silvia Giulia Galfrè¹, Valentina Silenzi^{1

2}, Erika Vitiello³, Davide Mariani³, Carmine Nicoletti⁴, Giulia Torromino⁵, Elvira De Leonibus^{5

6}, Julie Martone⁷, Irene Bozzoni^{1

2

3}

Affiliations

¹ Department of Biology and Biotechnologies "Charles Darwin", Sapienza University of Rome, 00185 Rome, Italy.
² Center for Life Nano- & Neuro-Science@Sapienza of Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy.
³ Center for Human Technologies (CHT) Istituto Italiano di Tecnologia (IIT), 16152 Genova, Italy.
⁴ DAHFMO - Section of Histology and Medical Embryology, Sapienza University of Rome, 00185 Rome, Italy.
⁵ Institute of Cellular Biology and Neurobiology "ABT", CNR, Monterotondo, 00015 Rome, Italy.
⁶ Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, 80078 Naples, Italy.
⁷ Institute of Molecular Biology and Pathology, CNR, 00185 Rome, Italy.

Abstract

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.

Keywords: Behavioral neuroscience; Molecular neuroscience; Neurogenetics.