ArticleInvestigative ophthalmology & visual science2009
An altered phenotype in a conditional knockout of Pitx2 in extraocular muscle.
Article in Investigative ophthalmology & visual science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Effects of fibroblast growth factor 2 on muscle precursor cells from mouse limb and extraocular muscle.PloS one · 2026Article
- Extreme Tolerance of Extraocular Muscles to Diseases and Aging: Why and How?International journal of molecular sciences · 2024Review
- Developmental, Physiological and Phylogenetic Perspectives on the Expression and Regulation of Myosin Heavy Chains in Craniofacial Muscles.International journal of molecular sciences · 2024Review
- TWIST1, a gene associated with Saethre-Chotzen syndrome, regulates extraocular muscle organization in mouse.Developmental biology · 2022Article
- Pitx genes in development and disease.Cellular and molecular life sciences : CMLS · 2021Review
- Mouse Extraocular Muscles and the Musculotopic Organization of Their Innervation.Anatomical record (Hoboken, N.J. : 2007) · 2019Article
- The ancient sarcomeric myosins found in specialized muscles.Skeletal muscle · 2019Review
- Requirement of Pitx2 for skeletal muscle homeostasis.Developmental biology · 2019Article
- Effects of retinoic acid signaling on extraocular muscle myogenic precursor cells in vitro.Experimental cell research · 2017Article
- Extraocular Muscle Repair and Regeneration.Current ophthalmology reports · 2017Article
- Sparing of the extraocular muscles in mdx mice with absent or reduced utrophin expression: A life span analysis.Neuromuscular disorders : NMD · 2015Article
- Muscle stem cells contribute to myofibres in sedentary adult mice.Nature communications · 2015Article
- Susceptibility of murine induced pluripotent stem cell-derived cardiomyocytes to hypoxia and nutrient deprivation.Stem cell research & therapy · 2015Article
- Pitx2, an atrial fibrillation predisposition gene, directly regulates ion transport and intercalated disc genes.Circulation. Cardiovascular genetics · 2014Article
- Dystrophic changes in extraocular muscles after gamma irradiation in mdx:utrophin(+/-) mice.PloS one · 2014Article
- The role of Pitx2 in maintaining the phenotype of myogenic precursor cells in the extraocular muscles.PloS one · 2013Article
- Dynamics of abducens nucleus neurons in the awake mouse.Journal of neurophysiology · 2012Article
- Genomic profiling reveals Pitx2 controls expression of mature extraocular muscle contraction-related genes.Investigative ophthalmology & visual science · 2012Article
- A zebrafish model of axenfeld-rieger syndrome reveals that pitx2 regulation by retinoic acid is essential for ocular and craniofacial development.Investigative ophthalmology & visual science · 2012Article
- Yeast two-hybrid analysis of a human trabecular meshwork cDNA library identified EFEMP2 as a novel PITX2 interacting protein.Molecular vision · 2012Article
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeTo 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.
methodsMouse 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.
resultsAll 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.
conclusionsPitx2 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.
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