scholarly journals Model Systems for Spinocerebellar Ataxias: Lessons Learned About the Pathogenesis

10.5772/27700 ◽  
2012 ◽  
Author(s):  
Thorsten Schmidt ◽  
Jana Schmidt ◽  
Jeannette Hbener
Keyword(s):  
Lessons Learned ◽  
Model Systems ◽  
Spinocerebellar Ataxias

scholarly journals Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 163
Author(s):  
Swapnil Gupta ◽  
Panpan You ◽  
Tanima SenGupta ◽  
Hilde Nilsen ◽  
Kulbhushan Sharma
Keyword(s):  
Dna Repair ◽  
Neurodegenerative Diseases ◽  
3D Models ◽  
Model Systems ◽  
Spinocerebellar Ataxias ◽  
C Elegans ◽  
Cellular Processes ◽  
Age Related ◽  
Damage Response ◽  
Lateral Sclerosis

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.

scholarly journals Strength in numbers: collaborative science for new experimental model systems

2018 ◽  
Author(s):  
Ross F. Waller ◽  
Phillip A. Cleves ◽  
Maria Rubio-Brotons ◽  
April Woods ◽  
Sara J. Bender ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Experimental Models ◽  
Lessons Learned ◽  
Model Systems ◽  
Model Organisms ◽  
Community Based ◽  
Collaborative Community ◽  
Important Challenge ◽  
Experimental Model Systems ◽  
Marine Protists

AbstractOur current understanding of biology is heavily based on the contributions from a small number of genetically tractable model organisms. Most eukaryotic phyla lack such experimental models, and this limits our ability to explore the molecular mechanisms that ultimately define their biology, ecology, and diversity. In particular, marine protists suffer from a paucity of model organisms despite playing critical roles in global nutrient cycles, food webs, and climate. To address this deficit, an initiative was launched in 2015 to foster development of ecologically and taxonomically diverse marine protist genetic models. This multifaceted, complex but important challenge required a highly collaborative community-based approach. Herein we describe this approach, the advances achieved, and the lessons learned by participants in this novel community-based model for research.

scholarly journals NvERTx: A gene expression database to compare Embryogenesis and Regeneration in the sea anemone Nematostella vectensis

2018 ◽  
Author(s):  
Jacob F. Warner ◽  
Vincent Guerlais ◽  
Aldine R. Amiel ◽  
Hereroa Johnston ◽  
Karine Nedoncelle ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Throughput ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Sea Anemone ◽  
Lessons Learned ◽  
Model Systems ◽  
Nematostella Vectensis ◽  
Gene Clustering ◽  
Gene Expression Database

AbstractFor more than a century researchers have been comparing embryogenesis and regeneration hoping that lessons learned from embryonic development will unlock hidden regenerative potential. This problem has historically been a difficult one to investigate since the best regenerative model systems are poor embryonic models and vice versa. Recently however, the comparison of embryogenesis and regeneration has seen renewed interest as emerging models including the sea anemone Nematostella vectensis have allowed researchers to investigate these processes in the same organism. This interest has been further fueled by the advent of high-throughput transcriptomic analyses that provide virtual mountains of data. Unfortunately much of this data remains in raw unanalyzed formats that are difficult to access or browse. Here we present NematostellavectensisEmbryogenesis and Regeneration Transcriptomics - NvERTx, the first platform for comparing gene expression during embryogenesis and regeneration. NvERTx is comprised of close to 50 RNAseq datasets spanning embryogenesis and regeneration in Nematostella. These data were used to perform a robust de novo transcriptome assembly which users can search, BLAST and plot expression of multiple genes during these two developmental processes. The site is also home to the results of gene clustering analyses, to further mine the data and identify groups of co-expressed genes. The site can be accessed at http://nvertx.kahikai.org.

scholarly journals Sorting Nexin 10 as a Key Regulator of Membrane Trafficking in Bone-Resorbing Osteoclasts: Lessons Learned From Osteopetrosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Ari Elson ◽  
Merle Stein ◽  
Grace Rabie ◽  
Maayan Barnea-Zohar ◽  
Sabina Winograd-Katz ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Lessons Learned ◽  
Model Systems ◽  
Bone Homeostasis ◽  
Sorting Nexin ◽  
Sequence Of Events ◽  
Ruffled Border ◽  
Regulated Gene Expression

Bone homeostasis is a complex, multi-step process, which is based primarily on a tightly orchestrated interplay between bone formation and bone resorption that is executed by osteoblasts and osteoclasts (OCLs), respectively. The essential physiological balance between these cells is maintained and controlled at multiple levels, ranging from regulated gene expression to endocrine signals, yet the underlying cellular and molecular mechanisms are still poorly understood. One approach for deciphering the mechanisms that regulate bone homeostasis is the characterization of relevant pathological states in which this balance is disturbed. In this article we describe one such “error of nature,” namely the development of acute recessive osteopetrosis (ARO) in humans that is caused by mutations in sorting nexin 10 (SNX10) that affect OCL functioning. We hypothesize here that, by virtue of its specific roles in vesicular trafficking, SNX10 serves as a key selective regulator of the composition of diverse membrane compartments in OCLs, thereby affecting critical processes in the sequence of events that link the plasma membrane with formation of the ruffled border and with extracellular acidification. As a result, SNX10 determines multiple features of these cells either directly or, as in regulation of cell-cell fusion, indirectly. This hypothesis is further supported by the similarities between the cellular defects observed in OCLs form various models of ARO, induced by mutations in SNX10 and in other genes, which suggest that mutations in the known ARO-associated genes act by disrupting the same plasma membrane-to-ruffled border axis, albeit to different degrees. In this article, we describe the population genetics and spread of the original arginine-to-glutamine mutation at position 51 (R51Q) in SNX10 in the Palestinian community. We further review recent studies, conducted in animal and cellular model systems, that highlight the essential roles of SNX10 in critical membrane functions in OCLs, and discuss possible future research directions that are needed for challenging or substantiating our hypothesis.

scholarly journals Mouse models of MLL leukemia: recapitulating the human disease

Blood ◽  
2017 ◽  
Vol 129 (16) ◽  
pp. 2217-2223 ◽  
Author(s):  
Thomas A. Milne
Keyword(s):  
Human Disease ◽  
Underlying Disease ◽  
Lessons Learned ◽  
New Drugs ◽  
Model Systems ◽  
Multiple Partner ◽  
Acute Leukemias ◽  
Chromosome Translocations ◽  
Animal Modeling ◽  
Wide Range

Abstract Chromosome translocations involving the mixed lineage leukemia (MLL) gene fuse it in frame with multiple partner genes creating novel fusion proteins (MLL-FPs) that cause aggressive acute leukemias in humans. Animal models of human disease are important for the exploration of underlying disease mechanisms as well as for testing novel therapeutic approaches. Patients carrying MLL-FPs have very few cooperating mutations, making MLL-FP driven leukemias ideal for animal modeling. The fact that the MLL-FP is the main driver mutation has allowed for a wide range of different experimental model systems designed to explore different aspects of MLL-FP leukemogenesis. In addition, MLL-FP driven acute myeloid leukemia (AML) in mice is often used as a general model for AML. This review provides an overview of different MLL-FP mouse model systems and discusses how well they have recapitulated aspects of the human disease as well as highlights the biological insights each model has provided into MLL-FP leukemogenesis. Many promising new drugs fail in the early stages of clinical trials. Lessons learned from past and present MLL-FP models may serve as a paradigm for designing more flexible and dynamic preclinical models for these as well as other acute leukemias.

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