Name: a quick phenotypic neurological scoring system for evaluating disease progression in the sod1-g93a mouse model of als
Uploaded: 2015-10-06T15:00:00
Description: Watch this Scientific Journal Video about A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS at JoVE.com

We would like to acknowledge Beth Levine for critically reviewing the manuscript, Valerie Tassinari for developing the genotyping protocol, and Matt Ferola and Carlos Maya for their exceptional animal care.

Alle forsøg udføres i overensstemmelse med de protokoller, der er beskrevet af National Institutes of Health Guide til pleje og anvendelse af dyr, og blev godkendt af ALS TDI institutionelle dyr pleje og brug udvalg (IACUC). 1. Dyr, Boliger og studiedesign Bemærk: SOD1 G93A-musekolonien blev afledt fra højt kopiantal B6SJLTgN (SOD1G93A) 1Gur stamme oprindeligt produceret af Gurney et al 7.. Kolonien er i færd med at blive opretholdt ved at ...

<ol>
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I denne rapport beskriver vi en hurtig og enkel video-protokol, som, hvis det anvendes korrekt, er i stand til pålideligt at vurdere sygdommens progression i SOD1-G93A mus og identificere lægemiddelinducerede ændringer. Mens forskellige grupper har udviklet fænotypiske pointsystemer for SOD1-G93A mus 8-10, de ofte ikke giver tilstrækkelige oplysninger om proceduren og er utilstrækkelige for replikation. Som følge heraf er pointsystemer sjældent anvendes uden den særlige gruppe, der udvikler dem. I de...

Lige siden dens udvikling i midten af 1990&#39;erne SOD1 G93A-transgene musemodel har været den mest udbredte dyremodel for amyotrofisk lateral sklerose (ALS) 1. Dette transgen musemodel blev gensplejset til at overudtrykke en mutant form af det humane Cu / Zn superoxiddismutase 1 (SOD1) genet, der huser ALS-associerede glycin til alanin-mutation ved aminosyre 93 (G93A). Den G93A mutationen er en af mange mutationer i SOD1 gen, som tilsammen make-up omkring en femtedel af familiære ALS tilfælde 2. Den SOD1-G93A model er blevet en arbejdshest af ALS lægemiddeludvikling forskning, fordi der ud over dens indlysende genetiske link til ALS, det sammenfatter mange af de patologiske funktioner i ALS hos mennesker såsom motorisk neuron tab, progressiv muskelsvaghed og atrofi, med eventuel lammelse og død 3. Dog, som det ofte er tilfældet med transgene dyremodeller, der er en iboende bigiske variation forbundet med SOD1 G93A-mus. Scott et al. har fastslået, at der er behov for kohorter af mindst 24 kuld-matchede køns- balanceret mus i lægemiddel-effektstudie designs for at overvinde den støj, skabt af den biologiske variabilitet 4. Det store antal dyr, der kræves i disse studier i kombination med den aggressive sygdomsprogression og behovet for daglig overvågning forbyder brugen af udførlige, tidskrævende og potentielt stressende teknikker til måling af neuromuskulær styrke og funktion (f.eks, elektromyografi, gribestyrke, roterende stang etc.). I stedet fremhæver det behovet for en in vivo screeningsværktøj, som pålideligt vurderer neuromuskulære funktion SOD1-G93A mus på en hurtig måde. På ALS TDI en protokol blev udviklet, der giver mulighed for pålidelig vurdering af den neuromuskulære funktion SOD1-G93A mus på mindre end 30 sek pr mus i gennemsnit. Denne protokol encompaSSES daglig vurdering af bagben funktion ved hjælp af en simpel neurologisk scoringssystem (NeuroScore), som er beskrevet i denne rapport i pressen og i video. NeuroScore er fokuseret på bagben funktion, fordi bagbenenes underskud er det tidligste rapporterede neurologiske tegn på sygdom i SOD1-G93A mus 5,6. Endvidere protokol udviklet af ALS TDI giver en objektiv vurdering af indtræden af ​​parese (let eller delvis paralyse), progression og sværhedsgraden af ​​lammelse og den er følsom nok til at identificere lægemiddelinducerede ændringer i sygdomsprogression.

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	<tbody>
		<tr>
			<td>B6SJLTgN(SOD1G93A)1Gur strain</td>
			<td>The Jackson Laboratory, Bar Harbor, ME</td>
			<td>002726</td>
			<td>Strain of mice used in this study</td>
		</tr>
		<tr>
			<td>Breeders</td>
			<td>Biomedical Research Models, Inc., Worcester, MA</td>
			<td></td>
			<td>Colony maintainance</td>
		</tr>
		<tr>
			<td>Scale</td>
			<td>Navigator OHAUS, Parsippany, NJ</td>
			<td>Model N14120</td>
			<td>Used to weigh mice</td>
		</tr>
		<tr>
			<td>Nutra-GelH</td>
			<td>Bio-Serv, Flemington, NJ</td>
			<td>#S4798</td>
			<td>Wet food provided to sick mice</td>
		</tr>
		<tr>
			<td>Irradiated Lab Animal Diet</td>
			<td>Harlan, Indianapolis, IN</td>
			<td>2918-111914M</td>
			<td>Chow diet</td>
		</tr>
		<tr>
			<td>Lab-grade Sani-chips</td>
			<td>Harlan Teklad, Indianapolis, IN</td>
			<td>7090</td>
			<td>Bedding</td>
		</tr>
		<tr>
			<td>JMPH&#160;</td>
			<td>SAS Institute, Inc., SAS Campus Drive, Cary, NC</td>
			<td>&#160;v10.0.2</td>
			<td>Statistical software</td>
		</tr>
		<tr>
			<td>Microsoft Excel</td>
			<td>Microsoft, One Microsoft Way, Redmond, WA</td>
			<td>Excel 2013 (v 15.0)</td>
			<td>Spreadsheet software</td>
		</tr>
		<tr>
			<td>GraphPad Prism 5</td>
			<td>GraphPad software Inc., La Jolla, CA</td>
			<td>v5.4</td>
			<td>Graphing software</td>
		</tr>
		<tr>
			<td>Mouse Huts</td>
			<td>Bio-Serv, Flemington, NJ</td>
			<td>K3272</td>
			<td>For environmental enrichment</td>
		</tr>
	</tbody>
</table>

a quick phenotypic neurological scoring system for evaluating disease progression in the sod1-g93a mouse model of als

The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening protocol, demonstrated in video herein, which reliably assesses the neuromuscular function of SOD1-G93A mice in a quick manner. This protocol encompasses a simple neurological scoring system (NeuroScore) designed to assess hindlimb function. NeuroScore is focused on hindlimb function because hindlimb deficits are the earliest reported neurological sign of disease in SOD1-G93A mice. The protocol developed by ALS TDI provides an unbiased assessment of onset of paresis (slight or partial paralysis), progression and severity of paralysis and it is sensitive enough to identify drug-induced changes in disease progression. In this report, the combination of a detailed manuscript with video minimizes scoring ambiguities and inter-experimenter variability thus allowing for the protocol to be adopted by other laboratories and enabling comparisons between studies taking place at different settings. We believe that this video protocol can serve as an excellent training tool for present and future ALS researchers.

De neurologiske score data for 90 mandlige og 94 kvindelige ikke-behandlede SOD1-G93A mus studerede på ALS TDI løbet 2014 blev evalueret. Resultaterne viser, at hanmus har typisk en mere aggressiv sygdomsprogression end hunmus, som det fremgår af en større andel af deres levetid på NS 1 i forhold til kvinder. NS 2 og 3 NS forekomme med praktisk taget lige store hyppighed uafhængigt af køn. NS 0 blev udelukket fra analysen, fordi det betragtes som en &quot;normal&quot; fænotype. NS 4 blev også udelukket, fordi p...

Watch this Scientific Journal Video about A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS at JoVE.com

A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS

This video protocol describes a sensitive, reliable, and quick method for evaluating the neuromuscular deficits in a transgenic mouse model of amyotrophic lateral sclerosis.

En hurtig Fænotypisk Neurologisk Scoring System til Evaluering Sygdom Progression i SOD1-G93A musemodel for ALS

The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening ...

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