Browsing by keyword "Alzheimer’s Disease Neuroimaging Initiative"

Now showing items 1-4 of 4

    • Age-dependent Changes in the Articular Cartilage and Subchondral Bone of C57BL/6 Mice after Surgical Destabilization of Medial Meniscus
      Huang, Henry; Skelly, Jordan D.; Ayers, David C.; Song, Jie (2017-02-09)
      Age is the primary risk factor for osteoarthritis (OA), yet surgical OA mouse models such as destabilization of the medial meniscus (DMM) used for evaluating disease-modifying OA targets are frequently performed on young adult mice only. This study investigates how age affects cartilage and subchondral bone changes in mouse joints following DMM. DMM was performed on male C57BL/6 mice at 4 months (4 M), 12 months (12 M) and 19+ months (19 M+) and on females at 12 M and 18 M+. Two months after surgery, operated and unoperated contralateral knees were harvested and evaluated using cartilage histology scores and muCT quantification of subchondral bone plate thickness and osteophyte formation. The 12 M and 19 M+ male mice developed more cartilage erosions and thicker subchondral bone plates after DMM than 4 M males. The size of osteophytes trended up with age, while the bone volume fraction was significantly higher in the 19 M+ group. Furthermore, 12 M females developed milder OA than males as indicated by less cartilage degradation, less subchondral bone plate sclerosis and smaller osteophytes. Our results reveal distinct age/gender-dependent structural changes in joint cartilage and subchondral bone post-DMM, facilitating more thoughtful selection of murine age/gender when using this surgical technique for translational OA research.

    • Exploring the erythroblastic island
      Socolovsky, Merav (2013-04-04)
      Two new studies suggest a crucial role for macrophages in boosting the number of red blood cells produced in vivo during stress, with translational implications for disease states such as β-thalassemia and polycythemia vera.

    • Gelsolin dysfunction causes photoreceptor loss in induced pluripotent cell and animal retinitis pigmentosa models
      Megaw, Roly; Abu-Arafeh, Hashem; Jungnickel, Melissa; Mellough, Carla; Gurniak, Christine; Witke, Walter; Zhang, Wei; Khanna, Hemant; Mill, Pleasantine; Dhillon, Baljean; et al. (2017-08-16)
      Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause X-linked RP (XLRP), an untreatable, inherited retinal dystrophy that leads to premature blindness. RPGR localises to the photoreceptor connecting cilium where its function remains unknown. Here we show, using murine and human induced pluripotent stem cell models, that RPGR interacts with and activates the actin-severing protein gelsolin, and that gelsolin regulates actin disassembly in the connecting cilium, thus facilitating rhodopsin transport to photoreceptor outer segments. Disease-causing RPGR mutations perturb this RPGR-gelsolin interaction, compromising gelsolin activation. Both RPGR and Gelsolin knockout mice show abnormalities of actin polymerisation and mislocalisation of rhodopsin in photoreceptors. These findings reveal a clinically-significant role for RPGR in the activation of gelsolin, without which abnormalities in actin polymerisation in the photoreceptor connecting cilia cause rhodopsin mislocalisation and eventual retinal degeneration in XLRP.Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause retinal dystrophy, but how this arises at a molecular level is unclear. Here, the authors show in induced pluripotent stem cells and mouse knockouts that RPGR mediates actin dynamics in photoreceptors via the actin-severing protein, gelsolin.

    • Orgo-Seq integrates single-cell and bulk transcriptomic data to identify cell type specific-driver genes associated with autism spectrum disorder
      Lim, Elaine T.; Chan, Yingleong; Dawes, Pepper; Erdin, Serkan; Reichert, Julia M.; Burns, Mannix J.; Church, George M. (2022-06-10)
      Cerebral organoids can be used to gain insights into cell type specific processes perturbed by genetic variants associated with neuropsychiatric disorders. However, robust and scalable phenotyping of organoids remains challenging. Here, we perform RNA sequencing on 71 samples comprising 1,420 cerebral organoids from 25 donors, and describe a framework (Orgo-Seq) to integrate bulk RNA and single-cell RNA sequence data. We apply Orgo-Seq to 16p11.2 deletions and 15q11-13 duplications, two loci associated with autism spectrum disorder, to identify immature neurons and intermediate progenitor cells as critical cell types for 16p11.2 deletions. We further applied Orgo-Seq to identify cell type-specific driver genes. Our work presents a quantitative phenotyping framework to integrate multi-transcriptomic datasets for the identification of cell types and cell type-specific co-expressed driver genes associated with neuropsychiatric disorders.