A phenotypic and molecular characterization of the fmr1-tm1Cgr fragile X mouse

Genes Brain Behav. 2004 Dec;3(6):337-59. doi: 10.1111/j.1601-183X.2004.00087.x.


Fragile X Syndrome is the most common form of inherited mental retardation. It is also known for having a substantial behavioral morbidity, including autistic features. In humans, Fragile X Syndrome is almost always caused by inactivation of the X-linked FMR1 gene. A single knockout mouse model, fmr1-tm1Cgr, exists. In this report we further characterize the cognitive and behavioral phenotype of the fmr1-tm1Cgr Fragile X mouse through the use of F1 hybrid mice derived from two inbred strains (FVB/NJ and C57BL/6J). Use of F1 hybrids allows focus on the effects of the fmr1-tm1Cgr allele with reduced influence from recessive alleles present in the parental inbred strains. We find that the cognitive phenotype of fmr1-tm1Cgr mice, including measures of working memory and learning set formation that are known to be seriously impacted in humans with Fragile X Syndrome, are essentially normal. Further testing of inbred strains supports this conclusion. Thus, any fmr1-tm1Cgr cognitive deficit is surprisingly mild or absent. There is, however, clear support presented for a robust audiogenic seizure phenotype in all strains tested, as well as increased entries into the center of an open field. Finally, a molecular examination of the fmr1-tm1Cgr mouse shows that, contrary to common belief, it is not a molecular null. Implications of this finding for interpretation of the phenotype are discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / genetics
  • Anxiety / physiopathology
  • Association Learning / physiology
  • Disease Models, Animal
  • Female
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / pathology
  • Fragile X Syndrome / physiopathology
  • Learning Disabilities / genetics*
  • Learning Disabilities / physiopathology
  • Male
  • Maze Learning / physiology*
  • Memory, Short-Term / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics*
  • Organ Size / genetics
  • Phenotype
  • RNA, Messenger / analysis
  • RNA-Binding Proteins / genetics*
  • Testis / anatomy & histology


  • Fmr1 protein, mouse
  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein