Neuroscience: Standard model

Schnabel, Jim

doi:10.1038/454682a

Cited by 73 publications

(43 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, natural polymorphic variant genes carried by wild-derived strains more closely resemble common human genetic variations than the genetic backgrounds of inbred mice, and these strains may thus better serve as models for understanding human complex biological systems such as the immune system 46 , as well as complex behaviours and polygenic complex diseases 9,47,48 . Thus wild-backcrossed mouse models should be seen as an important complementary tool, and possibly as a 'missing link' between laboratory-based mouse studies and genome-wide association studies in humans.…”

Section: Discussionmentioning

confidence: 99%

Mapping ecologically relevant social behaviours by gene knockout in wild mice

et al. 2014

View full text Add to dashboard Cite

The laboratory mouse serves as an important model system for studying gene, brain and behavioural interactions. Powerful methods of gene targeting have helped to decipher gene-function associations in human diseases. Yet, the laboratory mouse, obtained after decades of human-driven artificial selection, inbreeding, and adaptation to captivity, is of limited use for the study of fitness-driven behavioural responses that characterize the ancestral wild house mouse. Here, we demonstrate that the backcrossing of wild mice with knockout mutant laboratory mice retrieves behavioural traits exhibited exclusively by the wild house mouse, thereby unmasking gene functions inaccessible in the domesticated mutant model. Furthermore, we show that domestication had a much greater impact on females than on males, erasing many behavioural traits of the ancestral wild female. Hence, compared with laboratory mice, wild-derived mutant mice constitute an improved model system to gain insights into neuronal mechanisms underlying normal and pathological sexually dimorphic social behaviours.

show abstract

Section: Discussionmentioning

confidence: 99%

Mapping ecologically relevant social behaviours by gene knockout in wild mice

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In the case of Duchenne muscular dystrophy, the mdx mice have a mutated dystrophin gene similar to human patients, but the outcome is much less severe compared to the symptoms observed in patients 11 . The most widely used mouse model for amyotrophic lateral sclerosis, the SOD1 mice, so far disappointed in revealing insights into disease mechanisms and therapeutic approaches 12,13 . Therefore, spinal cord explants-muscle cell co-cultures to study the function, genomic and proteomic characteristics of the muscle coming from patients, in a completely physiological setting, represent an invaluable tool to study such complex diseases.…”

Section: Discussionmentioning

confidence: 99%

A Functional Motor Unit in the Culture Dish: Co-culture of Spinal Cord Explants and Muscle Cells

Arnold

Christe

Handschin

2012

JoVE

View full text Add to dashboard Cite

Human primary muscle cells cultured aneurally in monolayer rarely contract spontaneously because, in the absence of a nerve component, cell differentiation is limited and motor neuron stimulation is missing 1 . These limitations hamper the in vitro study of many neuromuscular diseases in cultured muscle cells. Importantly, the experimental constraints of monolayered, cultured muscle cells can be overcome by functional innervation of myofibers with spinal cord explants in co-cultures.Here, we show the different steps required to achieve an efficient, proper innervation of human primary muscle cells, leading to complete differentiation and fiber contraction according to the method developed by Askanas 2 . To do so, muscle cells are co-cultured with spinal cord explants of rat embryos at ED 13.5, with the dorsal root ganglia still attached to the spinal cord slices. After a few days, the muscle fibers start to contract and eventually become cross-striated through innervation by functional neurites projecting from the spinal cord explants that connecting to the muscle cells. This structure can be maintained for many months, simply by regular exchange of the culture medium.The applications of this invaluable tool are numerous, as it represents a functional model for multidisciplinary analyses of human muscle development and innervation. In fact, a complete de novo neuromuscular junction installation occurs in a culture dish, allowing an easy measurement of many parameters at each step, in a fundamental and physiological context. Just to cite a few examples, genomic and/or proteomic studies can be performed directly on the co-cultures. Furthermore, pre-and post-synaptic effects can be specifically and separately assessed at the neuromuscular junction, because both components come from different species, rat and human, respectively. The nerve-muscle co-culture can also be performed with human muscle cells isolated from patients suffering from muscle or neuromuscular diseases 3 , and thus can be used as a screening tool for candidate drugs. Finally, no special equipment but a regular BSL2 facility is needed to reproduce a functional motor unit in a culture dish. This method thus is valuable for both the muscle as well as the neuromuscular research communities for physiological and mechanistic studies of neuromuscular function, in a normal and disease context. Video LinkThe video component of this article can be found at http://www.jove.com/video/3616/ Protocol Establish the human muscle cell cultures according to the explantation-re-explantation technique 4 . First, remove non-muscle tissue from the biopsies. Then, embed 1 mm 3 muscle explants in a coagulum of plasma, which allows fibroblasts to emerge from the explants. 2. The embedded explants are transferred onto a plasma-gelatin coated dish and let them grow in normal growth medium (MEM supplemented with 25% medium 199, 10% fetal bovine serum [FBS], 1% penicillin/streptomycin, 10 μg/ml insulin, 10 ng/ml human epidermal growth factor [EGF], 12.5 ng/ml human f...

show abstract

“…Potential new treatments for conditions, such as amyotrophic lateral sclerosis, have proved to be beneficial in mouse transgenic models, but have failed to be of benefit in the clinical setting. 100 In other words, these models have had poor predictive validity with respect to drug treatments. 101 Some models may have good face validity with respect to the fidelity of the experimental versus clinical exposure (for example, animal models of schizophrenia related to prenatal infection), 102 but have poor face validity with respect to faithfully reproducing the surface-level phenotype of the clinical disorder of interest.…”

Section: Caveatsmentioning

confidence: 99%

Big ideas for small brains: what can psychiatry learn from worms, flies, bees and fish?

et al. 2010

View full text Add to dashboard Cite

While the research community has accepted the value of rodent models as informative research platforms, there is less awareness of the utility of other small vertebrate and invertebrate animal models. Neuroscience is increasingly turning to smaller, non-rodent models to understand mechanisms related to neuropsychiatric disorders. Although they can never replace clinical research, there is much to be learnt from 'small brains'. In particular, these species can offer flexible genetic 'tool kits' that can be used to explore the expression and function of candidate genes in different brain regions. Very small animals also offer efficiencies with respect to high-throughput screening programs. This review provides a concise overview of the utility of models based on worm, fruit fly, honeybee and zebrafish. Although these species may have small brains, they offer the neuropsychiatric research community opportunities to explore some of the most important research questions in our field.

show abstract

Neuroscience: Standard model

Abstract: Questions raised about the use of 'ALS mice' are prompting a broad reappraisal of the way that drugs are tested in animal models of neurodegenerative disease. Jim Schnabel reports.

Cited by 73 publications

References 7 publications

Mapping ecologically relevant social behaviours by gene knockout in wild mice

Mapping ecologically relevant social behaviours by gene knockout in wild mice

A Functional Motor Unit in the Culture Dish: Co-culture of Spinal Cord Explants and Muscle Cells

Big ideas for small brains: what can psychiatry learn from worms, flies, bees and fish?

Contact Info

Product

Resources

About