title: Genetic reduction of group 1 metabotropic glutamate receptors alters select behaviors in a mouse model for fragile X syndrome.
abstract: BACKGROUND
  Genetic heterogeneity likely contributes to variability in the symptoms among individuals with fragile X syndrome (FXS). Studies in the Fmr1 knockout (KO) mouse model for FXS suggest that excessive signaling through group I metabotropic glutamate receptors (Gp1 mGluRs), comprised of subtypes mGluR1 and mGluR5, may play a role. Hence, Gp1 mGluRs may act as modifiers of FXS. Currently no studies have addressed whether manipulation of mGluR1 activity may alter Fmr1 KO behavioral responses, and only a few have reported the effects of mGluR5 manipulation. Therefore, the goals for this study were to extend our understanding of the effects of modulating Gp1 mGluR activity on Fmr1 KO behavioral responses.
  
  
  METHODS
  The present study determined if genetically reducing mGluR1 or mGluR5 by 50% affects an extensive array of behaviors in the Fmr1 KO.
  
  
  RESULTS
  Reduction of mGluR1 moderately decreased Fmr1 KO activity. Reduction of mGluR5 caused an analgesic response in the Fmr1 KO and decreased active social behavior. Modulation of either mGluR1 or mGluR5 did not significantly alter audiogenic seizures, anxiety- and perseverative-related responses, sensorimotor gating, memory, or motor responses.
  
  
  CONCLUSIONS
  Genetic reduction of mGluR1 or mGluR5 modified a few select Fmr1 KO behaviors, although these modifications appeared to be subtle in nature and/or limited to select behaviors. This may indicate that 50% reduction of either mGluR1 or mGluR5 is insufficient to produce behavioral changes, and therefore, these receptors may not be dominant modifiers of a number of Fmr1 KO behavioral phenotypes.
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA. amthomas@bcm.edu
authors.forename: Alexia M
authors.initials: AM
authors.lastname: Thomas
authors.forename: Nghiem
authors.initials: N
authors.lastname: Bui
authors.forename: Deanna
authors.initials: D
authors.lastname: Graham
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Perkins
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Yuva-Paylor
authors.forename: Richard
authors.initials: R
authors.lastname: Paylor
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D015153:Blotting, Western; D003213:Conditioning, Psychological; D004195:Disease Models, Animal; D020195:Epilepsy, Reflex / Q000235:genetics / Q000523:psychology; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000523:psychology; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000235:genetics* / Q000523:psychology*; D005838:Genotype; D006358:Hot Temperature; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D010147:Pain Measurement / Q000523:psychology; D004856:Postural Balance / Q000235:genetics / Q000502:physiology; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis / Q000235:genetics*; D013216:Reflex, Startle / Q000502:physiology; D013737:Testis / Q000033:anatomy & histology / Q000502:physiology
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C497684:Fmr1 protein, mouse; C578936:Grm5 protein, mouse; C104077:metabotropic glutamate receptor type 1