Postadolescent changes in regional cerebral protein synthesis: an in vivo study in the FMR1 null mouse.
Methylation-induced transcriptional silencing of the fragile X mental retardation-1 (Fmr1) gene leads to absence of the gene product, fragile X mental retardation protein (FMRP), and consequently fragile X syndrome (FrX), an X-linked inherited form of mental retardation. Absence of FMRP in Fmr1 null mice imparts some characteristics of the FrX phenotype, but the precise role of FMRP in neuronal function remains unknown. FMRP is an RNA-binding protein that has been shown to suppress translation of certain mRNAs in vitro. We applied the quantitative autoradiographic L-[1-14C]leucine method to the in vivo determination of regional rates of cerebral protein synthesis (rCPS) in adult wild-type (WT) and Fmr1 null mice at 4 and 6 months of age. Our results show a substantial decrease in rCPS in all brain regions examined between the ages of 4 and 6 months in both WT and Fmr1 null mice. Superimposed on the age-dependent decline in rCPS, we demonstrate a regionally selective elevation in rCPS in Fmr1 null mice. Our results suggest that the process of synaptic pruning during young adulthood may be reflected in decreased rCPS. Our findings support the hypothesis that FMRP is a suppressor of translation in brain in vivo.
Qin
Mei
M
Laboratory of Cerebral Metabolism, National Institute of Mental Health, United States Public Health Service, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
Kang
Julia
J
Burlin
Thomas V
TV
Jiang
Chunhui
C
Smith
Carolyn Beebe
CB
D000367:Age Factors; D000818:Animals; D001345:Autoradiography / Q000379:methods; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000502:physiology*; D005600:Fragile X Syndrome / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007930:Leucine / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000502:physiology; D009929:Organ Size / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D013997:Time Factors; D014316:Tritium / Q000378:metabolism
D051860:Fragile X Messenger Ribonucleoprotein 1; D007930:Leucine; D014316:Tritium; C497684:Fmr1 protein, mouse