FENS Forum of European Neuroscience edition:7 location:Amsterdam date:3 - 7 july 2010
Mature mRNA is exported from the nucleus to the cytoplasm, where it is translated into protein. Nuclear export involves the assembly of the mRNA into large messenger ribonucleoprotein complexes. The prime member of the family of nuclear RNA export factor (NXF) proteins, NXF1, plays a key role in this process. However, the function of NXF2, NXF3 and NXF5 are not yet clear. In contrast to NXF1, mouse Nxf7 and its human homologue NXF5 are localized prominently in the cytoplasm and have been associated with polysomes, stress granules and processing bodies (P-bodies), indicating that Nxf7 plays a crucial role in mRNA sorting, transport and/or storage (1). Nxf7 is prominently expressed in day 7.5 embryo as well as in the adult mouse brain, including the cortex and hippocampus. Furthermore, we reported that disruption of the human homologue NXF5 is associated with a syndromic form of X-linked mental retardation in a male patient (2, 3).
To understand how the absence of NXF5 leads to mental retardation, we generated an Nxf7 deficient mouse model and evaluated the behavioral phenotype in male Nxf7 knockout (Nxf7 /-) and wild type (WT) littermates. No gross anatomical differences were observed between Nxf7-/- and WT mice. Nxf7-/- displayed a deficit in hippocampus-dependent spatial learning in the Morris water maze. At the synaptic level, electrophysiological recordings from the hippocampal CA1 region in vitro, Nxf7-/- and WT mice showed no differences in fast synaptic transmission. However, Nxf7-/- displayed changes in paired pulse facilitation and theta burst-induced long-term potentiation.
We report that disruption of Nxf7 in mouse leads to impairment in hippocampus-dependent learning and NMDA-dependent synaptic plasticity, which might contribute to the mental illness in our patient.
1) Katahira et al., (2008) Nucleic Acids Res, 36(2):616-28.
2) Jun et al., (2005) Curr Biol 11(18):1381-91
3) Frints et al., (2003) Am J Med Genet A, 119A(3):367-74