Altered mossy fiber distributions in adult Fmr1 (FVB) knockout mice.
The fragile-X mental retardation protein (FMRP) is greatly reduced or absent in individuals with fragile-X mental retardation syndrome, a common, heritable form of mental retardation. Morphological studies suggest that this protein functions in normal synapse maturation and neuronal plasticity. Examination of human brain autopsy tissue has shown that fragile-X patients exhibit long, thin spines more frequently, and stubby mushroom-shaped spines less frequently, than these two types of spines are seen in normal autopsy tissue. Fragile-X tissue also has a greater density of these spines along dendrites, which suggests a possible failure of synapse elimination. Fmr1 knockout mice and wild-type littermates brains were processed for Timm staining, which reveals the zinc-rich terminals of the dentate gyrus, the mossy fibers. The Fmr1 knockout mice exhibited a pattern of Timm granule-staining within the stratum oriens of subfield CA3 and the inner molecular layer that was significantly different than staining seen in wild-type animals. The sources and consequences of the altered terminal staining are unclear, but are discussed in relation to immature synapse morphology, a failure of normal regression of synapses, and a potential biological penalty of such a failure to regress.
Ivanco
Tammy L
TL
Beckman Institute, University of Illinois, Urbana 61801, USA. ivancotl@ms.umanitoba.ca
Greenough
William T
WT
D000818:Animals; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D016601:RNA-Binding Proteins; D013194:Staining and Labeling; D013569:Synapses / Q000473:pathology
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse