Gpm6b deficiency impairs sensorimotor gating and modulates the behavioral response to a 5-HT2A/C receptor agonist.
The neuronal tetraspan proteins, M6A (Gpm6a) and M6B (Gpm6b), belong to the family of proteolipids that are widely expressed in the brain. We recently reported Gpm6a deficiency as a monogenetic cause of claustrophobia in mice. Its homolog proteolipid, Gpm6b, is ubiquitously expressed in neurons and oligodendrocytes. Gpm6b is involved in neuronal differentiation and myelination. It interacts with the N-terminal domain of the serotonin transporter (SERT) and decreases cell-surface expression of SERT. In the present study, we employed Gpm6b null mutant mice (Gpm6b(-/-)) to search for behavioral functions of Gpm6b. We studied male and female Gpm6b(-/-) mice and their wild-type (WT, Gpm6b(+/+)) littermates in an extensive behavioral test battery. Additionally, we investigated whether Gpm6b(-/-) mice exhibit changes in the behavioral response to a 5-HT2A/C receptor agonist. We found that Gpm6b(-/-) mice display completely normal sensory and motor functions, cognition, as well as social and emotionality-like (anxiety, depression) behaviors. On top of this inconspicuous behavioral profile, Gpm6b(-/-) mice of both genders exhibit a selective impairment in prepulse inhibition of the acoustic startle response. Furthermore, in contrast to WT mice that show the typical locomotion suppression and increase in grooming activity after intraperitoneal administration of DOI [(±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride], Gpm6b(-/-) mice demonstrate a blunted behavioral response to this 5-HT2A/C receptor agonist. To conclude, Gpm6b deficiency impairs sensorimotor gating and modulates the behavioral response to a serotonergic challenge.
Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany; DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
Ekrem
E
Dere
Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Daniela
D
Winkler
Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Caroline
C
Ritter
Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Anja
A
Ronnenberg
Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Giulia
G
Poggi
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Julia
J
Patzig
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany.
Manuela
M
Gernert
Department of Psychiatry & Psychotherapy, University of Erlangen, Germany.
Christian
C
Müller
DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany; Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Klaus-Armin
KA
Nave
Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany; DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany. Electronic address: ehrenreich@em.mpg.de.
Hannelore
H
Ehrenreich
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Hauke B
HB
Werner
D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D055139:Sensory Gating / Q000502:physiology*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism
C083481:Gpm6b protein, mouse; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D050486:Serotonin Plasma Membrane Transport Proteins
C57BL/6J; Glycoprotein M6B; Gpm6a; Prepulse inhibition; Proteolipid protein (PLP); Serotonin transporter (SERT)