Improving Reproducibility of Phenotypic Assessments in the DyW Mouse Model of Laminin-alpha2 Related Congenital Muscular Dystrophy

Raffaella Willmann, Heather Gordish-Dressman, Sarina Meinen, Markus A. Ruegg, Qing Yu, Kanneboyina Nagaraju, Ayar Kumar, Mahasweta Girgenrath, Caroline B.M. Coffey, Vivian Cruz, Pam M. Van Ry, Laurent Bogdanik, Cathleen Lutz, Anne Rutkowski, Dean J. Burkin

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Abstract

Laminin-α2 related Congenital Muscular Dystrophy (LAMA2-CMD) is a progressive muscle disease caused by partial or complete deficiency of laminin-211, a skeletal muscle extracellular matrix protein. In the last decade, basic science research has queried underlying disease mechanisms in existing LAMA2-CMD murine models and identified possible clinical targets and pharmacological interventions. Experimental rigor in preclinical studies is critical to efficiently and accurately quantify both negative and positive results, degree of efficiency of potential therapeutics and determine whether to move a compound forward for additional preclinical testing. In this review, we compare published available data measured to assess three common parameters in the widely used mouse model DyW, that mimics LAMA2-CMD, we quantify variability and analyse its possible sources. Finally, on the basis of this analysis, we suggest standard set of assessments and the use of available standardized protocols, to reduce variability of outcomes in the future and to improve the value of preclinical research.
Original languageEnglish
Pages (from-to)115-126
JournalJournal of neuromuscular diseases
Volume4
Issue number2
DOIs
Publication statusPublished - 24 May 2017

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Muscular Dystrophies
Laminin
Muscle Proteins
Extracellular Matrix Proteins
Research
Skeletal Muscle
Pharmacology
Muscles
Therapeutics

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Willmann, Raffaella ; Gordish-Dressman, Heather ; Meinen, Sarina ; Ruegg, Markus A. ; Yu, Qing ; Nagaraju, Kanneboyina ; Kumar, Ayar ; Girgenrath, Mahasweta ; Coffey, Caroline B.M. ; Cruz, Vivian ; Van Ry, Pam M. ; Bogdanik, Laurent ; Lutz, Cathleen ; Rutkowski, Anne ; Burkin, Dean J. / Improving Reproducibility of Phenotypic Assessments in the DyW Mouse Model of Laminin-alpha2 Related Congenital Muscular Dystrophy. In: Journal of neuromuscular diseases. 2017 ; Vol. 4, No. 2. pp. 115-126.
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abstract = "Laminin-α2 related Congenital Muscular Dystrophy (LAMA2-CMD) is a progressive muscle disease caused by partial or complete deficiency of laminin-211, a skeletal muscle extracellular matrix protein. In the last decade, basic science research has queried underlying disease mechanisms in existing LAMA2-CMD murine models and identified possible clinical targets and pharmacological interventions. Experimental rigor in preclinical studies is critical to efficiently and accurately quantify both negative and positive results, degree of efficiency of potential therapeutics and determine whether to move a compound forward for additional preclinical testing. In this review, we compare published available data measured to assess three common parameters in the widely used mouse model DyW, that mimics LAMA2-CMD, we quantify variability and analyse its possible sources. Finally, on the basis of this analysis, we suggest standard set of assessments and the use of available standardized protocols, to reduce variability of outcomes in the future and to improve the value of preclinical research.",
author = "Raffaella Willmann and Heather Gordish-Dressman and Sarina Meinen and Ruegg, {Markus A.} and Qing Yu and Kanneboyina Nagaraju and Ayar Kumar and Mahasweta Girgenrath and Coffey, {Caroline B.M.} and Vivian Cruz and {Van Ry}, {Pam M.} and Laurent Bogdanik and Cathleen Lutz and Anne Rutkowski and Burkin, {Dean J.}",
year = "2017",
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Willmann, R, Gordish-Dressman, H, Meinen, S, Ruegg, MA, Yu, Q, Nagaraju, K, Kumar, A, Girgenrath, M, Coffey, CBM, Cruz, V, Van Ry, PM, Bogdanik, L, Lutz, C, Rutkowski, A & Burkin, DJ 2017, 'Improving Reproducibility of Phenotypic Assessments in the DyW Mouse Model of Laminin-alpha2 Related Congenital Muscular Dystrophy', Journal of neuromuscular diseases, vol. 4, no. 2, pp. 115-126. https://doi.org/10.3233/JND-170217

Improving Reproducibility of Phenotypic Assessments in the DyW Mouse Model of Laminin-alpha2 Related Congenital Muscular Dystrophy. / Willmann, Raffaella; Gordish-Dressman, Heather; Meinen, Sarina; Ruegg, Markus A.; Yu, Qing; Nagaraju, Kanneboyina; Kumar, Ayar; Girgenrath, Mahasweta; Coffey, Caroline B.M.; Cruz, Vivian; Van Ry, Pam M.; Bogdanik, Laurent; Lutz, Cathleen; Rutkowski, Anne; Burkin, Dean J.

In: Journal of neuromuscular diseases, Vol. 4, No. 2, 24.05.2017, p. 115-126.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Improving Reproducibility of Phenotypic Assessments in the DyW Mouse Model of Laminin-alpha2 Related Congenital Muscular Dystrophy

AU - Willmann, Raffaella

AU - Gordish-Dressman, Heather

AU - Meinen, Sarina

AU - Ruegg, Markus A.

AU - Yu, Qing

AU - Nagaraju, Kanneboyina

AU - Kumar, Ayar

AU - Girgenrath, Mahasweta

AU - Coffey, Caroline B.M.

AU - Cruz, Vivian

AU - Van Ry, Pam M.

AU - Bogdanik, Laurent

AU - Lutz, Cathleen

AU - Rutkowski, Anne

AU - Burkin, Dean J.

PY - 2017/5/24

Y1 - 2017/5/24

N2 - Laminin-α2 related Congenital Muscular Dystrophy (LAMA2-CMD) is a progressive muscle disease caused by partial or complete deficiency of laminin-211, a skeletal muscle extracellular matrix protein. In the last decade, basic science research has queried underlying disease mechanisms in existing LAMA2-CMD murine models and identified possible clinical targets and pharmacological interventions. Experimental rigor in preclinical studies is critical to efficiently and accurately quantify both negative and positive results, degree of efficiency of potential therapeutics and determine whether to move a compound forward for additional preclinical testing. In this review, we compare published available data measured to assess three common parameters in the widely used mouse model DyW, that mimics LAMA2-CMD, we quantify variability and analyse its possible sources. Finally, on the basis of this analysis, we suggest standard set of assessments and the use of available standardized protocols, to reduce variability of outcomes in the future and to improve the value of preclinical research.

AB - Laminin-α2 related Congenital Muscular Dystrophy (LAMA2-CMD) is a progressive muscle disease caused by partial or complete deficiency of laminin-211, a skeletal muscle extracellular matrix protein. In the last decade, basic science research has queried underlying disease mechanisms in existing LAMA2-CMD murine models and identified possible clinical targets and pharmacological interventions. Experimental rigor in preclinical studies is critical to efficiently and accurately quantify both negative and positive results, degree of efficiency of potential therapeutics and determine whether to move a compound forward for additional preclinical testing. In this review, we compare published available data measured to assess three common parameters in the widely used mouse model DyW, that mimics LAMA2-CMD, we quantify variability and analyse its possible sources. Finally, on the basis of this analysis, we suggest standard set of assessments and the use of available standardized protocols, to reduce variability of outcomes in the future and to improve the value of preclinical research.

U2 - 10.3233/JND-170217

DO - 10.3233/JND-170217

M3 - Article

VL - 4

SP - 115

EP - 126

JO - Journal of neuromuscular diseases

JF - Journal of neuromuscular diseases

SN - 2214-3599

IS - 2

ER -