Meny

Javascript verkar inte påslaget? - Vissa delar av Lunds universitets webbplats fungerar inte optimalt utan javascript, kontrollera din webbläsares inställningar.
Du är här

An Altered Phenotype in a Conditional Knockout of Pitx2 in Extraocular Muscle

Författare:
  • Yuefang Zhou
  • Georgiana Cheng
  • Lisa Dieter
  • Tord Hjalt
  • Francisco H. Andrade
  • John S. Stahl
  • Henry J. Kaminski
Publiceringsår: 2009
Språk: Engelska
Sidor: 4531-4541
Publikation/Tidskrift/Serie: Investigative Ophthalmology & Visual Science
Volym: 50
Nummer: 10
Dokumenttyp: Artikel
Förlag: Association for Research in Vision and Ophthalmology Inc

Sammanfattning

PURPOSE. To determine the temporal and spatial expression of Pitx2, a bicoid-like homeobox transcription factor, during postnatal development of mouse extraocular muscle and to evaluate its role in the growth and phenotypic maintenance of postnatal extraocular muscle. METHODS. Mouse extraocular muscles of different ages were examined for the expression of Pitx2 by RT-PCR, q-PCR, and immunostaining. A conditional mutant mouse strain, in which Pitx2 function is inactivated at postnatal day (P)0, was generated with a Cre-loxP strategy. Histology, immunostaining, real-time PCR, in vitro muscle contractility, and in vivo ocular motility were used to study the effect of Pitx2 depletion on extraocular muscle. RESULTS. All three Pitx2 isoforms were expressed by extraocular muscle and at higher levels than in other striated muscles. Immunostaining demonstrated the presence of Pitx2 mainly in extraocular muscle myonuclei. However, no obvious expression patterns were observed in terms of anatomic region (orbital versus global layer), innervation zone, or muscle fiber types. The mutant extraocular muscle had no obvious pathology but had altered muscle fiber sizes. Expression levels of myosin isoforms Myh1, Myh6, Myh7, and Myh13 were reduced, whereas Myh2, Myh3, Myh4, and Myh8 were not affected by postnatal loss of Pitx2. In vitro, Pitx2 loss made the extraocular muscles stronger, faster, and more fatigable. Eye movement recordings found saccades to have a lower peak velocity. CONCLUSIONS. Pitx2 is important in maintaining the mature extraocular muscle phenotype and regulating the expression of critical contractile proteins. Modulation of Pitx2 expression can influence extraocular muscle function with long-term therapeutic implications. (Invest Ophthalmol Vis Sci. 2009; 50: 4531-4541) DOI:10.1167/iovs.08-2950

Disputation

Nyckelord

  • Medicine and Health Sciences

Övriga

Published
Yes
  • ISSN: 0146-0404

Box 117, 221 00 LUND
Telefon 046-222 00 00 (växel)
Telefax 046-222 47 20
lu [at] lu [dot] se

Fakturaadress: Box 188, 221 00 LUND
Organisationsnummer: 202100-3211
Om webbplatsen