The study investigates the abnormal dendritic spines in fragile X knockout mice, focusing on maturation and pruning deficits. Key findings include: 1. **Dendritic Spine Length and Density**: - Knockout mice exhibit significantly longer dendritic spines compared to wild-type control animals (t = 2.25, df = 6, P = 0.033). - The density of dendritic spines along the apical dendrites of layer V pyramidal cells is substantially greater in knockout mice (F₁,₃₃ = 63.3; P < 0.0001). 2. **Spine Morphology**: - Knockout mice show an increased prevalence of thin, elongated spines and fewer short spines. - The density of long, thin spines is higher in knockout mice, suggesting a deficit in the normal selection or "pruning" of synaptic contacts during development. 3. **Discussion**: - The observed morphology and density of dendritic spines in knockout mice resemble those seen during early synaptogenesis and following sensory deprivation. - The increased number of long, thin spines and spine density suggest a deficit in the normal maturation and pruning processes. - These findings implicate the Fmr1 gene and its associated protein, FMRP, in the developmental processes leading to normal adult dendritic spine morphology and number. - FMRP is synthesized locally at synapses in response to synaptic activity, and its synthesis may play a role in synapse maturation and the selection-elimination process. - The altered dendritic spine morphology and density, along with behavioral deficits and macroorchidism, suggest that the knockout mice may be an excellent model for human fragile X syndrome and provide a new system for studying synaptic maturation and stabilization. The study supports the idea that FMRP plays a crucial role in the development of adult synaptic architecture and highlights the importance of further research to understand its cellular functions.The study investigates the abnormal dendritic spines in fragile X knockout mice, focusing on maturation and pruning deficits. Key findings include: 1. **Dendritic Spine Length and Density**: - Knockout mice exhibit significantly longer dendritic spines compared to wild-type control animals (t = 2.25, df = 6, P = 0.033). - The density of dendritic spines along the apical dendrites of layer V pyramidal cells is substantially greater in knockout mice (F₁,₃₃ = 63.3; P < 0.0001). 2. **Spine Morphology**: - Knockout mice show an increased prevalence of thin, elongated spines and fewer short spines. - The density of long, thin spines is higher in knockout mice, suggesting a deficit in the normal selection or "pruning" of synaptic contacts during development. 3. **Discussion**: - The observed morphology and density of dendritic spines in knockout mice resemble those seen during early synaptogenesis and following sensory deprivation. - The increased number of long, thin spines and spine density suggest a deficit in the normal maturation and pruning processes. - These findings implicate the Fmr1 gene and its associated protein, FMRP, in the developmental processes leading to normal adult dendritic spine morphology and number. - FMRP is synthesized locally at synapses in response to synaptic activity, and its synthesis may play a role in synapse maturation and the selection-elimination process. - The altered dendritic spine morphology and density, along with behavioral deficits and macroorchidism, suggest that the knockout mice may be an excellent model for human fragile X syndrome and provide a new system for studying synaptic maturation and stabilization. The study supports the idea that FMRP plays a crucial role in the development of adult synaptic architecture and highlights the importance of further research to understand its cellular functions.