Mouse models of ALS: Past, present and future

  title={Mouse models of ALS: Past, present and future},
  author={Cathleen Lutz},
  journal={Brain Research},
  • C. Lutz
  • Published 1 August 2018
  • Biology
  • Brain Research

Nearly 30 Years of Animal Models to Study Amyotrophic Lateral Sclerosis: A Historical Overview and Future Perspectives

The up to date and available ALS genetic animal models are described, classified by the different genetic mutations and divided per species, pointing out their features in modeling, the onset and progression of the pathology, as well as their specific pathological hallmarks.

SOD1-targeting therapies for neurodegenerative diseases: a review of current findings and future potential

A literature search of publications pertaining to SOD1-ALS and its treatment from 1992-present using the MEDLINE database form the basis for this review.

Animal models of amyotrophic lateral sclerosis: a comparison of model validity

The zebrafish model of environmentally-induced motor neuron degeneration displays convincing features of face validity with many hallmarks of ALS-like features, and weakness in construct validity; however, the value of this model may lie in its potential to be more representative of the pathogenic features underlying sporadic ALS cases.

Cell-based Research and Therapy for Amyotrophic Lateral Sclerosis: Promises and Challenges

Cell therapy is emerging as a promising therapeutic alternative for ALS and the advent of induced pluripotent stem cells (iPSCs) has enabled the development of patient-specific cell lines, a valuable tool to investigate in vitro molecular mechanisms of the disease and therapies in different genetic backgrounds.

Harnessing the Potential of Human Pluripotent Stem Cell-Derived Motor Neurons for Drug Discovery in Amyotrophic Lateral Sclerosis: From the Clinic to the Laboratory and Back to the Patient

Almost 2 decades of research in the field is reviewed, first highlighting the steps required to efficiently generate MNs from human ESCs and iPSCs that led to the identification of compounds currently being tested in clinical trials for ALS and discussing the potential and caveats of using patient iPSC-derived MNs as a platform for drug screening.

Modeling ALS using iPSCs: Is it possible to reproduce the phenotypic variations observed in patients in vitro?

The pathophysiological markers detected in cells differentiated from iPSCs of ALS patients are summarized and could be useful for drug screening, through stratifying patients according to their genetic background.

Genetically modified mice for research on human diseases: A triumph for Biotechnology or a work in progress?

The biotechnology for creating genetically modified mice which reflect these factors and how they might be used to discover new treatments for complex human diseases such as cancers, neurodevelopmental and neurodegenerative diseases are examined.

Locus-specific analysis of Transposable Elements during the progression of ALS in the SOD1G93A mouse model

It is shown that TEs become up-regulated at the early stages of the disease, and via statistical associations, it is speculated that they can regulate several genes, which in turn might be contributing to the genetic dysfunction observed in ALS.

P2X7 Receptor Antagonism as a Potential Therapy in Amyotrophic Lateral Sclerosis

This review focuses on the purinergic ionotropic receptor P2X7 (P2X7R) as a potential target for developing drugs that delay the onset and/or disease progression in patients with amyotrophic lateral



Pathogenesis of FUS-associated ALS and FTD: insights from rodent models

The evidence for FUS pathogenicity in ALS/FTD is discussed, the experimental approaches used and phenotypic features of FUS rodent models reported to date are reviewed, and their contribution to the understanding of pathogenic mechanisms are outlined.

Design, power, and interpretation of studies in the standard murine model of ALS

  • Sean ScottJ. E. Kranz J. Heywood
  • Biology
    Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases
  • 2008
The majority of published effects are most likely measurements of noise in the distribution of survival means as opposed to actual drug effect, so a minimum study design is recommended for this mouse model to best address and manage this inherent noise.

Gene discovery in amyotrophic lateral sclerosis: implications for clinical management

It is observed that many gene variants associated with ALS have effect sizes between those of mutations that greatly increase risk and those of common variants that have a small effect on risk, and this observation is combined with insights from next-generation sequencing to explore the implications for genetic counselling.

Progress in Therapy Development for Amyotrophic Lateral Sclerosis

Current trends in experimental therapeutics for ALS are explored with emphasis on the emerging interest in axon guidance signaling pathways as novel targets for pharmacological support of neural cytoskeletal structure and function in order to slow ALS.

NEK1 mutations in familial amyotrophic lateral sclerosis.

The association between NEK1 variants and familial ALS was assessed using whole exome sequence data of 265 familial ALS index patients and 827 control individuals to assess the variant burden inNEK1.

A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity

These unique mice allow us to further the understanding of ALS by separating the central motor neuron body degeneration and the peripheral effects from a fALS mutation expressed at endogenous levels.

Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

A moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS found several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene.