Laminins and Congenital Muscular Dystrophy - From a Mouse Model to Gene Therapy of Laminin alpha2 chain deficiency?

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

Sammanfattning

Gene therapy holds great promise for treating many genetic diseases, including muscular dystrophies. Mutations in the gene encoding laminin alpha2 chain ? an extracellular protein prominently expressed in the neuromuscular system ? cause a severe neuromuscular disorder: congenital muscular dystrophy type 1A (MDC1A). Currently, there is no treatment for MDC1A. Preclinical studies are the first step in testing genetic approaches for future gene therapy in humans. In the course of my research, I focused on a genetically manipulated mouse model of MDC1A, investigating whether the transgenic introduction of laminin ?1 chain into laminin alpha2 chain deficient tissues would prevent the development of disease symptoms.

The overexpression of laminin alpha1 chain greatly improved overall health and normalized the life span of laminin alpha2 chain deficient animals. Laminin alpha1 chain, which in the adult body is expressed only in a few epithelial tissues, functionally compensated for laminin alpha2 chain loss in muscle, peripheral nervous system and testis, correcting their morphology and restoring their function. Moreover, laminin alpha1 chain proved to be essential for the normal expression levels of laminin receptors dystroglycan and integrin alpha7 in laminin alpha2 chain deficient muscle. I suggest that our preclinical studies with laminin alpha1 chain transgene may serve as a paradigm for gene therapy of congenital muscular dystrophy in patients.
Originalspråkengelska
KvalifikationDoktor
Tilldelande institution
  • Institutionen för experimentell medicinsk vetenskap
Handledare
  • Durbeej-Hjalt, Madeleine, handledare
Tilldelningsdatum2006 dec. 9
Förlag
ISBN (tryckt)91-85559-55-5
StatusPublished - 2006

Bibliografisk information

Defence details

Date: 2006-12-09
Time: 09:00
Place: Biomedical Centre, Sölvegatan 19 GK Salen

External reviewer(s)

Name: Ruegg, Marcus
Title: Professor
Affiliation: University of Basel, Switzerland

---


<div class="article_info">Kinga Gawlik, Yuko Miyagoe-Suzuki, Peter Ekblom, Shin'ichi Takeda and Madeleine Durbeej. <span class="article_issue_date">2004</span>. <span class="article_title">Laminin alpha1 chain reduces muscular dystrophy in laminin alpha2 chain deficient mice</span> <span class="journal_series_title">Human Molecular Genetics</span>, <span class="journal_volume">vol 13</span> <span class="journal_pages">pp 1775-1784</span>.</div>
<div class="article_info">Mattias Häger, Kinga Gawlik, Alexander Nyström, Takako Sasaki and Madeleine Durbeej. <span class="article_issue_date">2005</span>. <span class="article_title">Laminin alpha1 chain corrects male infertility caused by absence of laminin alpha2 chain</span> <span class="journal_series_title">American Journal of Pathology</span>, <span class="journal_volume">vol 167</span> <span class="journal_pages">pp 823-833</span>.</div>
<div class="article_info">Kinga Gawlik, Jia-Yi Li, Åsa Petersen and Madeleine Durbeej. <span class="article_issue_date">2006</span>. <span class="article_title">Laminin alpha1 chain improves laminin alpha2 chain deficient peripheral neuropathy</span> <span class="journal_series_title">Human Molecular Genetics</span>, <span class="journal_volume">vol 15</span> <span class="journal_pages">pp 2690-2700</span>.</div>
<div class="article_info">Kinga Gawlik, Ulrike Mayer, Kristina Blomberg, Arnoud Sonnenberg, Peter Ekblom and Madeleine Durbeej. <span class="article_issue_date">2006</span>. <span class="article_title">Laminin alpha1 chain mediated reduction of laminin alpha2 chain deficient muscular dystrophy involves integrin alpha7 beta1 and dystroglycan</span> <span class="journal_series_title">FEBS Letters</span>, <span class="journal_volume">vol 580</span> <span class="journal_pages">pp 1759-1765</span>.</div>

Ämnesklassifikation (UKÄ)

  • Medicinska grundvetenskaper

Fingeravtryck

Utforska forskningsämnen för ”Laminins and Congenital Muscular Dystrophy - From a Mouse Model to Gene Therapy of Laminin alpha2 chain deficiency?”. Tillsammans bildar de ett unikt fingeravtryck.

Citera det här