Fmr1 Knockout Mice: A Model to Study Fragile X Mental Retardation. The Dutch-Belgian Fragile X Consortium

Cell. 1994 Jul 15;78(1):23-33.

Abstract

Male patients with fragile X syndrome lack FMR1 protein due to silencing of the FMR1 gene by amplification of a CGG repeat and subsequent methylation of the promoter region. The absence of FMR1 protein leads to mental retardation, aberrant behavior, and macroorchidism. Hardly anything is known about the physiological function of FMR1 and the pathological mechanisms leading to these symptoms. Therefore, we designed a knockout model for the fragile X syndrome in mice. The knockout mice lack normal Fmr1 protein and show macroorchidism, learning deficits, and hyperactivity. Consequently, this knockout mouse may serve as a valuable tool in the elucidation of the physiological role of FMR1 and the mechanisms involved in macroorchidism, abnormal behavior, and mental retardation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Behavior, Animal
  • Brain / pathology
  • Disease Models, Animal*
  • Female
  • Fertility
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome* / genetics
  • Fragile X Syndrome* / metabolism
  • Fragile X Syndrome* / pathology
  • Fragile X Syndrome* / psychology
  • Humans
  • Male
  • Mental Processes
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / physiology
  • Organ Size
  • Phenotype
  • Purkinje Cells / pathology
  • Pyramidal Cells / pathology
  • RNA-Binding Proteins*
  • Testis / pathology

Substances

  • FMR1 protein, human
  • Fmr1 protein, mouse
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein