TY  - JOUR
AB  - Duchenne muscular dystrophy (DMD) is a fatal X-linked disease caused by mutations in the DMD gene, leading to complete absence of dystrophin and progressive degeneration of skeletal muscles and heart. Animal models are essential for preclinical evaluation of novel diagnostic procedures and treatment strategies. Gene targeting/editing offers the possibility of developing tailored pig models for monogenic diseases. The first porcine DMD model was generated by deletion of DMD exon 52 (DMDΔ52) in cultured kidney cells, which were used for somatic cell nuclear transfer to produce DMDΔ52 offspring. The animals resembled clinical, biochemical, and pathological hallmarks of DMD, but died before sexual maturity, thus preventing their propagation by breeding. This limitation was overcome by the generation of female heterozygous DMDΔ52 carrier pigs, which allowed the establishment of a large breeding colony. In this overview, we summarize how porcine DMD models have been used for dissecting disease mechanisms, for validating multispectral optoacoustic tomography as an imaging modality for monitoring fibrosis, and for preclinical testing of a CRISPR/Cas9 based approach to restore an intact DMD reading frame. Particular advantages of porcine DMD models include their targeted design and the rapid disease progression with early cardiac involvement, facilitating translational studies in reasonable time frames.
AU  - Stirm, M.*
AU  - Fonteyne, L.M.*
AU  - Shashikadze, B.*
AU  - Stöckl, J.B.*
AU  - Kurome, M.*
AU  - Keßler, B.*
AU  - Zakhartchenko, V.*
AU  - Kemter, E.*
AU  - Blum, H.*
AU  - Arnold, G.J.*
AU  - Matiasek, K.*
AU  - Wanke, R.*
AU  - Wurst, W.
AU  - Nagashima, H.*
AU  - Knieling, F.*
AU  - Walter, M.C.*
AU  - Kupatt, C.*
AU  - Fröhlich, T.*
AU  - Klymiuk, N.*
AU  - Blutke, A.*
AU  - Wolf, E.*
C1  - 65468
C2  - 52697
SP  - 543-556
TI  - Pig models for Duchenne muscular dystrophy - from disease mechanisms to validation of new diagnostic and therapeutic concepts.
JO  - Neuromusc. Disord.
VL  - 32
IS  - 7
PY  - 2022
SN  - 0960-8966
ER  - 

TY  - JOUR
AU  - Prokisch, H.
C1  - 54078
C2  - 45289
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
SP  - S3-S4
TI  - Molecular diagnostics of Mendelian disorders via RNA sequencing.
JO  - Neuromusc. Disord.
VL  - 28
PB  - Pergamon-elsevier Science Ltd
PY  - 2018
SN  - 0960-8966
ER  - 

TY  - JOUR
AB  - Mutant genes associated with Charcot Marie Tooth type 2, distal hereditary motor neuropathy and familial amyotrophic lateral sclerosis may cause overlapping clinical phenotypes. We performed whole genome linkage analysis, haplotype analysis, sequencing and detailed clinical and neurophysiological investigations in a large Norwegian kindred with a condition that clinically had been classified as Charcot Marie Tooth type 2. The mutation c.140A>G, p.His47Arg (alias p.His46Arg or H46R) in the superoxide dismutase 1 gene (SOD1) segregated with the disease. The patients present a hereditary motor neuropathy-like clinical picture and long survival (mean 29 years). To our knowledge, this is the first extensive report describing a large non-Japanese kindred. The prognostic implications of the condition seen in this family have little in common with what is normally associated with sporadic amyotrophic lateral sclerosis and illustrates the complexity of the genetic etiology of lower motor neuron disease.
AU  - Ostern, R.*
AU  - Fagerheim, T.*
AU  - Orstavik, K.*
AU  - Holmoy, T.*
AU  - Heiberg, A.*
AU  - Lund-Petersen, I.*
AU  - Strom, T.M.
AU  - Nilssen, O.*
AU  - Dahl, A.*
C1  - 7608
C2  - 29893
SP  - 511-521
TI  - Hereditary motor neuron disease in a large Norwegian family with a "H46R" substitution in the superoxide dismutase 1 gene.
JO  - Neuromusc. Disord.
VL  - 22
IS  - 6
PB  - Pergamon-elsevier Science Ltd
PY  - 2012
SN  - 0960-8966
ER  -