title: Behavioral characterization of striatal-enriched protein tyrosine phosphatase (STEP) knockout mice.
abstract: Striatal-enriched protein tyrosine phosphatase (STEP) has been described as a regulator of multiple kinases and glutamate receptor subunits critical for synaptic plasticity. Published behavioral and biochemical characterization from the founder line of STEP knockout (KO) mice revealed superior cognitive performance, with enhanced phosphorylation of substrates such as ERK, Fyn and GluN2B; suggesting that inhibitors of STEP may have potential as therapeutic agents for the treatment of neuropsychiatric disorders. The objectives of this work aimed to replicate and extend the previously reported behavioral consequences of STEP knockout. Consistent with previous reported data, STEP KO mice demonstrated exploratory activity levels and similar motor coordination relative to WT littermate controls as well as intact memory in a Y-maze spatial novelty test. Interestingly, KO mice demonstrated deficits in pre-pulse inhibition as well as reduced seizure threshold relative to WT controls. Immunohistochemical staining of brains revealed the expected gene-dependent reduction in STEP protein confirming knockout in the mice. The present data confirm expression and localization of STEP and the absence in KO mice, and describe functional downstream implications of reducing STEP levels in vivo.
authors.affiliation: Neuroscience Research Unit, Pfizer Research & Development, Cambridge, MA, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Sukoff Rizzo
authors.forename: S M
authors.initials: SM
authors.lastname: Lotarski
authors.forename: P
authors.initials: P
authors.lastname: Stolyar
authors.forename: T
authors.initials: T
authors.lastname: McNally
authors.forename: C
authors.initials: C
authors.lastname: Arturi
authors.forename: M
authors.initials: M
authors.lastname: Roos
authors.forename: J E
authors.initials: JE
authors.lastname: Finley
authors.forename: V
authors.initials: V
authors.lastname: Reinhart
authors.forename: T A
authors.initials: TA
authors.lastname: Lanz
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology / Q000503:physiopathology; D005106:Exploratory Behavior; D008124:Locomotion; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D010433:Pentylenetetrazole / Q000633:toxicity; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology
chemical_list: D054558:Protein Tyrosine Phosphatases, Non-Receptor; C082101:Ptpn5 protein, mouse; D010433:Pentylenetetrazole
keywords: Behavioral phenotype; KO mice; NMDA; STEP; schizophrenia