Complete cloning of the duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals

Kœnig, M.; Hoffman, Eric P.; Bertelson, Corlee J.; Monaco, Anthony P.; Feener, Chris A.; Kunkel, Louis M.

doi:10.1016/0092-8674(87)90504-6

Cited by 2,157 publications

(1,140 citation statements)

References 37 publications

Supporting

Mentioning

1,068

Contrasting

Unclassified

Order By: Relevance

“…Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by loss of dystrophin protein expression that leads to the wasting of skeletal muscles [1,2]. mdx mice are a commonly used model for testing therapeutic approaches to DMD; mdx animals do not express dystrophin protein in most of their skeletal myofibers, and mdx myofibers exhibit several important pathological hallmarks of DMD [3,4].…”

Section: Introductionmentioning

confidence: 99%

Postnatal overexpression of the CT GalNAc transferase inhibits muscular dystrophy in mdx mice without altering muscle growth or neuromuscular development: Evidence for a utrophin-independent mechanism

Camboni

Martin

2007

Neuromuscular Disorders

View full text Add to dashboard Cite

Overexpression of the cytotoxic T cell (CT) GalNAc transferase (Galgt2) in the skeletal muscles of transgenic mdx mice inhibits the development of muscular dystrophy. The profound effect of Galgt2 on muscular dystrophy in transgenic mice, where overexpression is begins from embryonic stages, is complicated by its additional effects on muscle growth and neuromuscular structure. Here, we use Adeno-associated virus (AAV) to show that overexpression of Galgt2 in skeletal myofibers in the early postnatal period is equally effective in inhibiting muscular dystrophy, but that it does so without altering muscle growth or neuromuscular structure. Unlike embryonic overexpression, postnatal overexpression of Galgt2 did not reproducibly increase the expression of utrophin, synaptic laminins, or dystrophin-associated glycoproteins along infected myofibers. Moreover, Galgt2 overexpression inhibited muscular dystrophy to the same extent in utrophin-deficient mdx muscles as it did in utrophin-expressing mdx muscles. Thus, Galgt2 is a molecular target for therapy in DMD that can be utilized in a manner that separates its clinical benefit from its effects on development, and its clinical benefit is distinct from that achieved by utrophin.

show abstract

Section: Introductionmentioning

confidence: 99%

Postnatal overexpression of the CT GalNAc transferase inhibits muscular dystrophy in mdx mice without altering muscle growth or neuromuscular development: Evidence for a utrophin-independent mechanism

Camboni

Martin

2007

Neuromuscular Disorders

View full text Add to dashboard Cite

show abstract

“…Deletions were detected in 72~o (13/18) of the DMD patients and in the one BMD patient. This detection rate was rather higher than that of 25~ in DMD and 50~ in BMD for the Japanese population as a whole (Asano et al, 1990), resembling the high detection rate in Caucasians ( Koenig et al, 1987). The discrepancy might be explained by our small sample size--especially for BMD (one case).…”

Section: Jpn D Human Genetmentioning

confidence: 51%

“…However, the usefulness of this probe may vary in the Japanese population, since RFLPs differ in their fragment sizes and allele frequencies depending on ethnic origin (Wainseoat et al, 1986). Koenig et al (1987) have cloned cDNA fragments of the DMD megagene spanning 2,000 kb at the Xp21 locus. Submicroscopic deletions were reportedly detected in about 60 ~o of DMD/BMD patients using such cDNA probes (Koenig et al, 1987;Forrest et al, 1987;Read et al, 1988;Worton and Thompson, 1988;Darras et al, 1988;Lieehti-Gallati et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

“…Koenig et al (1987) have cloned cDNA fragments of the DMD megagene spanning 2,000 kb at the Xp21 locus. Submicroscopic deletions were reportedly detected in about 60 ~o of DMD/BMD patients using such cDNA probes (Koenig et al, 1987;Forrest et al, 1987;Read et al, 1988;Worton and Thompson, 1988;Darras et al, 1988;Lieehti-Gallati et al, 1989). However, sufficient data has not been accumulated regarding RFLPs and deletion studies in Japanese DMD/BMD families (Akita et al, 1987;Sugino et al, 1989;Asano et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

DNA analysis of Duchenne and Becker muscular dystrophy using pERT87 genomic probes and dystrophin cDNA probes

Ubagai

Katayama

1991

Jap J Human Genet

View full text Add to dashboard Cite

SummaryDNA analysis was performed on 19 unrelated Duchenne muscular dystrophy (DMD) families and one Becker muscular dystrophy (BMD) family in Japan to determine their carrier status. The intragenic genomic probe pERT87 with its subclones 87-1, 87-8, and 87-15 were used together with five eDNA probes from the 5' end of the dystrophin gene.The tests With both a high polymorphism information content (P.I.C.) and a high observed P.LC. were most effective, i.e., pERT87-1/XmnI, pERT87-15/ XmnI, pERT87-8/TaqI, and pERT87-8/BstXI. These test combinations were useful in the Japanese population but pERT87-15/TaqI was not, although it was effective in Caucasians. Two additional test combinations of pERT87-1/MspI and pERT87-15/BamHI were highly useful in detecting restriction fragment length polymorphisms (RFLPs) when other tests were not informative. Carrier status could be determined in 18 out of 20 clients who were at risk for DMD/BMD carrier status from 20 families, similar to the rate of detection in Caucasians. The total detection rate of deletions was 74 ~ with the five eDNA probes. Deletions were concentrated on two hot spots where 92 ~ of all deletions were detected by only two probes, 1-2a and 8. Deletions were detected in two males with DMD who had none of the eight RFLPs tested. Our results emphasize the usefulness of DNA analysis with pERT87 genomic probes and cDNA probes. In addition, an optimum strategy for carrier detection in Japanese DMD/BMD families was proposed.

show abstract

“…DMD is caused by mutations in the dystrophin gene ( DMD ) and the resulting reduction of dystrophin protein 2, 3. Dystrophin is a 427 kDa, multidomain protein primarily found in skeletal and cardiac muscle.…”

mentioning

confidence: 99%

Anisomycin Activates Utrophin Upregulation Through a p38 Signaling Pathway

Hadwen

Farooq

Witherspoon

et al. 2018

Clinical Translational Sci

View full text Add to dashboard Cite

Duchenne muscular dystrophy is a recessive X‐linked disease characterized by progressive muscle wasting; cardiac or respiratory failure causes death in most patients by the third decade. The disease is caused by mutations in the dystrophin gene that lead to a loss of functional dystrophin protein. Although there are currently few treatments for Duchenne muscular dystrophy, previous reports have shown that upregulating the dystrophin paralog utrophin in Duchenne muscular dystrophy mouse models is a promising therapeutic strategy. We conducted in silico mining of the Connectivity Map database for utrophin‐inducing agents, identifying the p38‐activating antibiotic anisomycin. Treatments of C2C12, undifferentiated murine myoblasts, and mdx primary myoblasts with anisomycin conferred increases in utrophin protein levels through p38 pathway activation. Anisomycin also induced utrophin protein levels in the diaphragm of mdx mice. Our study shows that repositioning small molecules such as anisomycin may prove to have Duchenne muscular dystrophy clinical utility.

show abstract

Complete cloning of the duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals

Cited by 2,157 publications

References 37 publications

Postnatal overexpression of the CT GalNAc transferase inhibits muscular dystrophy in mdx mice without altering muscle growth or neuromuscular development: Evidence for a utrophin-independent mechanism

Postnatal overexpression of the CT GalNAc transferase inhibits muscular dystrophy in mdx mice without altering muscle growth or neuromuscular development: Evidence for a utrophin-independent mechanism

DNA analysis of Duchenne and Becker muscular dystrophy using pERT87 genomic probes and dystrophin cDNA probes

Anisomycin Activates Utrophin Upregulation Through a p38 Signaling Pathway

Contact Info

Product

Resources

About