Материал из hpluswiki
Перейти к навигации Перейти к поиску

Fragile X mental retardation syndrome-related protein 1 (hFXR1p)


Fxr1 knockout mice show a striated muscle phenotype: implications for Fxr1p function in vivo.

FXR1 is one of the two known homologues of FMR1. FXR1 shares a high degree of sequence homology with FMR1 and also encodes two KH domains and an RGG domain, conferring RNA-binding capabilities. In comparison with FMRP, very little is known about the function of FXR1P in vivo. Mouse knockout (KO) models exist for both Fmr1 and Fxr2. To study the function of Fxr1 in vivo, we generated an Fxr1 KO mouse model. Homozygous Fxr1 KO neonates die shortly after birth most likely due to cardiac or respiratory failure. Histochemical analyses carried out on both skeletal and cardiac muscles show a disruption of cellular architecture and structure in E19 Fxr1 neonates compared with wild-type (WT) littermates. In WT E19 skeletal and cardiac muscles, Fxr1p is localized to the costameric regions within the muscles. In E19 Fxr1 KO littermates, in addition to the absence of Fxr1p, costameric proteins vinculin, dystrophin and alpha-actinin were found to be delocalized. A second mouse model (Fxr1 neo), which expresses strongly reduced levels of Fxr1p relative to WT littermates, does not display the neonatal lethal phenotype seen in the Fxr1 KOs but does display a strongly reduced limb musculature and has a reduced life span of approximately 18 weeks. The results presented here point towards a role for Fxr1p in muscle mRNA transport/translation control similar to that seen for Fmrp in neuronal cells.

MeSH Terms

  • Animals
  • Cytoskeletal Proteins
  • Fragile X Mental Retardation Protein
  • Hindlimb
  • Longevity
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal
  • Myocardium
  • Nerve Tissue Proteins
  • Protein Structure, Tertiary
  • RNA, Messenger
  • RNA-Binding Proteins
  • Sequence Homology

Developmental expression of the fragile X-related 1 proteins in mouse testis: association with microtubule elements.

Fragile X mental retardation 1 protein (FMRP) is the archetype of a class of cytoplasmic mRNA-binding proteins that includes the fragile X-related 1 and 2 proteins (FXR1P and FXR2P). Whereas absence of FMRP is the cause of fragile X syndrome, it is not known if FXR1P and FXR2P are associated with any pathology. It is also still elusive whether these homologous proteins can partially compensate for the absence of FMRP in the case of the fragile X syndrome. FXR1 is widely expressed in mammals and its expression pattern is complex since several mRNA variants and protein isoforms are detected. In mouse, we observed that the highest level of FXR1 is found in the adult testis. This tissue is an exception, since all known FXR1P isoforms, some of which have been considered as tissue specific, are detected in it. In young animals, changes in mRNA-spliced variants and their corresponding protein isoforms occur during spermatogenesis. Using biochemical, immunohistochemical and electron microscopic techniques, we show that FXR1P is associated with microtubule elements. Since the cytoskeletal framework is implicated in cellular plasticity as well as in mRNA transport, we propose new possibilities for the function(s) of the FXR proteins.

MeSH Terms

  • Aging
  • Animals
  • Blotting, Northern
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression
  • Immunoblotting
  • Immunoenzyme Techniques
  • Liver
  • Male
  • Mice
  • Microtubule-Associated Proteins
  • Microtubules
  • Polymerase Chain Reaction
  • Polyribosomes
  • Protein Isoforms
  • RNA, Messenger
  • RNA-Binding Proteins
  • Sperm Tail
  • Spermatocytes
  • Spermatogenesis
  • Testis
  • Transcription, Genetic