Mouse behavioral endophenotypes for schizophrenia.
An endophenotype is a heritable trait that is generally considered to be more highly, associated with a gene-based neurological deficit than a disease phenotype itself. Such, endophenotypic deficits may therefore be observed in the non-affected relatives of disease patients. Once endophenotypes have been established for a given illness, such as schizophrenia, mechanisms of, action may then be established and treatment options developed in order to target such measures. The, current paper describes and assesses the merits and limitations of utilizing behavioral and, electrophysiological endophenotypes of schizophrenia in mice. Such endophenotypic deficits include: decreased auditory event related potential (ERP) amplitude and gating (specifically, that of the P20, N40, P80 and P120); impaired mismatch negativity (MMN); changes in theta and gamma frequency, analyses; decreased pre-pulse inhibition (PPI); impaired working and episodic memories (for instance, novel object recognition [NOR], contextual and cued fear conditioning, latent inhibition, Morris and, radial arm maze identification and nose poke); sociability; and locomotor activity. A variety of, pharmacological treatments, including ketamine, MK-801 and phencyclidine (PCP) can be used to, induce some of the deficits described above, and numerous transgenic mouse strains have been, developed to address the mechanisms responsible for such endophenotypic differences. We also, address the viability and validity of using such measures regarding their potential clinical implications, and suggest several practices that could increase the translatability of preclinical data.
Amann
Laura C
LC
Stanley Medical Research Institute for Experimental Therapeutics, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, United States.
Gandal
Michael J
MJ
Halene
Tobias B
TB
Ehrlichman
Richard S
RS
White
Samantha L
SL
McCarren
Hilary S
HS
Siegel
Steven J
SJ
D000161:Acoustic Stimulation; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D004195:Disease Models, Animal; D058068:Endophenotypes; D006801:Humans; D007266:Inhibition, Psychological; D007859:Learning Disabilities / Q000209:etiology; D008569:Memory Disorders / Q000209:etiology; D051379:Mice; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*