Reversal of sensorimotor gating abnormalities in Fmr1 knockout mice carrying a human Fmr1 transgene.

Fragile X syndrome is caused by a CGG trinucleotide repeat expansion of the FMR1 gene. Individuals with fragile X display several behavioral abnormalities including hyperactivity, social anxiety, autistic-like features, impaired cognitive processing, and impaired sensorimotor gating. The Fmr1KO mouse model of fragile X exhibits several related behavioral phenotypes such as increased activity and altered social interactions. Individuals with fragile X also have impaired sensorimotor gating as measured using the prepulse inhibition of startle response. The authors have recently shown that Fmr1KO mice with a yeast artificial chromosome containing the human FMR1 gene have corrected or overcorrected abnormal behaviors including hyperactivity and altered social interactions. Here the authors present results from a study examining abnormal sensorimotor gating in Fmr1KO mice. Consistent with previous findings, Fmr1KO mice have increased prepulse inhibition. The KO mice with the yeast artificial chromosome containing the human FMR1 gene had levels of prepulse inhibition comparable to WT mice, indicating not only a correction of this phenotype, but also clearly demonstrating that in mice levels of the fragile X mental retardation protein regulate sensorimotor gating.

[1]  D. Nelson,et al.  Social behavior in Fmr1 knockout mice carrying a human FMR1 transgene. , 2008, Behavioral neuroscience.

[2]  D. Hessl,et al.  Brief Report: Aggression and Stereotypic Behavior in Males with Fragile X Syndrome—Moderating Secondary Genes in a “Single Gene” Disorder , 2008, Journal of autism and developmental disorders.

[3]  D. Flood,et al.  Variables affecting prepulse inhibition of the startle reflex and the response to antipsychotics in DBA/2NCrl mice , 2007, Psychopharmacology.

[4]  T. Nabeshima,et al.  Neural Circuits Containing Pallidotegmental GABAergic Neurons are Involved in the Prepulse Inhibition of the Startle Reflex in Mice , 2007, Biological Psychiatry.

[5]  Deborah D. Hatton,et al.  ADHD symptoms in children with FXS , 2006, American journal of medical genetics. Part A.

[6]  Deborah D. Hatton,et al.  Autistic behavior in children with fragile X syndrome: Prevalence, stability, and the impact of FMRP , 2006, American journal of medical genetics. Part A.

[7]  R. Paylor,et al.  Fmr1 knockout mice are impaired in a leverpress escape/avoidance task , 2006, Genes, brain, and behavior.

[8]  D. Nelson,et al.  Exaggerated behavioral phenotypes in Fmr1/Fxr2 double knockout mice reveal a functional genetic interaction between Fragile X-related proteins. , 2006, Human molecular genetics.

[9]  Wim E. Crusio,et al.  Social behavior deficits in the Fmr1 mutant mouse , 2006, Behavioural Brain Research.

[10]  R. Paylor,et al.  Altered anxiety‐related and social behaviors in the Fmr1 knockout mouse model of fragile X syndrome , 2005, Genes, brain, and behavior.

[11]  E. De Schutter,et al.  Deletion of FMR1 in Purkinje Cells Enhances Parallel Fiber LTD, Enlarges Spines, and Attenuates Cerebellar Eyelid Conditioning in Fragile X Syndrome , 2005, Neuron.

[12]  S. Puglisi‐Allegra,et al.  Object recognition impairment in Fmr1 knockout mice is reversed by amphetamine: involvement of dopamine in the medial prefrontal cortex , 2004, Behavioural pharmacology.

[13]  Alcino J. Silva,et al.  Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice , 2004, Molecular Psychiatry.

[14]  M. Geyer,et al.  Mouse genetic models for prepulse inhibition: an early review , 2002, Molecular Psychiatry.

[15]  Stephen T Warren,et al.  A decade of molecular studies of fragile X syndrome. , 2002, Annual review of neuroscience.

[16]  Darci M. Nielsen,et al.  Alterations in the auditory startle response in Fmr1 targeted mutant mouse models of fragile X syndrome , 2002, Brain Research.

[17]  L. Chen,et al.  Fragile X mice develop sensory hyperreactivity to auditory stimuli , 2001, Neuroscience.

[18]  Deborah D. Hatton,et al.  Variability in FMRP and early development in males with fragile X syndrome. , 2001, American journal of mental retardation : AJMR.

[19]  Stephan Eliez,et al.  Functional brain activation during cognition is related to FMR1 gene expression , 2000, Brain Research.

[20]  D. Nelson,et al.  (Over)correction of FMR1 deficiency with YAC transgenics: behavioral and physical features. , 2000, Human molecular genetics.

[21]  P. Jin,et al.  Understanding the molecular basis of fragile X syndrome. , 2000, Human molecular genetics.

[22]  B. Oostra,et al.  FMRP expression as a potential prognostic indicator in fragile X syndrome. , 1999, American journal of medical genetics.

[23]  J. Crawley,et al.  Inbred strain differences in prepulse inhibition of the mouse startle response , 1997, Psychopharmacology.

[24]  R. D'Hooge,et al.  Mildly impaired water maze performance in maleFmr1 knockout mice , 1997, Neuroscience.

[25]  N. Swerdlow,et al.  Prepulse inhibition in the rat is regulated by ventral and caudodorsal striato-pallidal circuitry. , 1995, Behavioral neuroscience.

[26]  R. D'Hooge,et al.  Fmr1 knockout mice: A model to study fragile X mental retardation , 1994, Cell.

[27]  W. Brown,et al.  Analysis of neocortex in three males with the fragile X syndrome. , 1991, American journal of medical genetics.

[28]  Silverman,et al.  Fragile X Syndrome Diagnosis Treatment And Research , 2016 .