{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T09:01:52Z","timestamp":1773392512579,"version":"3.50.1"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although fetal breathing movements are required for normal lung development, there is uncertainty concerning the specific effect of absent fetal breathing movements on pulmonary cell maturation. We set out to evaluate pulmonary development in a genetically defined mouse model, the myogenin null mouse, in which there is a lack of normal skeletal muscle fibers and thus skeletal muscle movements are absent in utero. Significant decreases were observed in lung:body weight ratio and lung total DNA at embryonic days (E)14, E17, and E20. Reverse transcriptase\/polymerase chain reaction, in situ immunofluorescence, and electron microscopy revealed early lung cell differentiation in both null and wild-type lungs as early as E14. However at E14, myogenin null lungs had decreased 5\u2032-bromo-2-deoxyuridine incorporation compared with that of wild-type littermates, whereas at E17 and E20, increased Bax immunolabeling and terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining were detected in the myogenin null mice but not in the wild-type littermates. These observations highlight the importance of skeletal muscle contractile activity in utero for normal lung organogenesis. Null mice lacking the muscle-specific transcription factor myogenin exhibit a secondary effect on lung development such that decreased lung cell proliferation and increased programmed cell death are associated with lung hypoplasia.<\/jats:p>","DOI":"10.1165\/ajrcmb.22.3.3708","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T21:39:08Z","timestamp":1365025148000},"page":"304-315","source":"Crossref","is-referenced-by-count":38,"title":["Pulmonary Hypoplasia in the\n                    <i>myogenin<\/i>\n                    Null Mouse Embryo"],"prefix":"10.1093","volume":"22","author":[{"given":"Brian S.","family":"Tseng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sash T.","family":"Cavin","sequence":"additional","affiliation":[{"name":"Departments of Neurology, and Integrative Biology, Pharmacology, and Physiology, University of Texas at Houston Medical School; Department of Molecular Pathology, M. D. Anderson Cancer Center, University of Texas Health Science Center, Houston; Department of Molecular Biology and Oncology, Hamon Center for Basic Research in Cancer, University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank W.","family":"Booth","sequence":"additional","affiliation":[{"name":"Departments of Neurology, and Integrative Biology, Pharmacology, and Physiology, University of Texas at Houston Medical School; Department of Molecular Pathology, M. D. Anderson Cancer Center, University of Texas Health Science Center, Houston; Department of Molecular Biology and Oncology, Hamon Center for Basic Research in Cancer, University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric N.","family":"Olson","sequence":"additional","affiliation":[{"name":"Departments of Neurology, and Integrative Biology, Pharmacology, and Physiology, University of Texas at Houston Medical School; Department of Molecular Pathology, M. D. Anderson Cancer Center, University of Texas Health Science Center, Houston; Department of Molecular Biology and Oncology, Hamon Center for Basic Research in Cancer, University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Carmen","family":"Marin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J.","family":"McDonnell","sequence":"additional","affiliation":[{"name":"Departments of Neurology, and Integrative Biology, Pharmacology, and Physiology, University of Texas at Houston Medical School; Department of Molecular Pathology, M. D. Anderson Cancer Center, University of Texas Health Science Center, Houston; Department of Molecular Biology and Oncology, Hamon Center for Basic Research in Cancer, University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian J.","family":"Butler","sequence":"additional","affiliation":[{"name":"Departments of Neurology, and Integrative Biology, Pharmacology, and Physiology, University of Texas at Houston Medical School; Department of Molecular Pathology, M. D. Anderson Cancer Center, University of Texas Health Science Center, Houston; Department of Molecular Biology and Oncology, Hamon Center for Basic Research in Cancer, University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,3,1]]},"reference":[{"key":"2026030700084838800_B1"},{"key":"2026030700084838800_B2","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0095-5108(18)30205-7","article-title":"The effects of mechanical forces on fetal lung growth.","volume":"23","author":"Kitterman","year":"1996","journal-title":"Clin. Perinat."},{"key":"2026030700084838800_B3"},{"key":"2026030700084838800_B4","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/S0140-6736(82)90986-2","article-title":"Is fetal respiratory function a major determinant of perinatal survival?","volume":"1","author":"Wigglesworth","year":"1982","journal-title":"Lancet"},{"key":"2026030700084838800_B5"},{"key":"2026030700084838800_B6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/oxfordjournals.bmb.a071237","article-title":"Fetal breathing.","volume":"31","author":"Boddy","year":"1975","journal-title":"Br. Med. Bull."},{"key":"2026030700084838800_B7","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1542\/peds.72.6.857","article-title":"Fetal akinesia deformation sequence: an animal model.","volume":"72","author":"Moessinger","year":"1983","journal-title":"Pediatrics"},{"key":"2026030700084838800_B8","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/S0022-3476(05)83148-8","article-title":"Early-onset respiratory failure caused by severe congenital neuromuscular disease.","volume":"124","author":"Sandler","year":"1994","journal-title":"J. Pediatr."},{"key":"2026030700084838800_B9","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1001\/archneur.1992.00530320083015","article-title":"Early predictors of poor outcome in congenital fiber-type disproportion myopathy.","volume":"49","author":"Torres","year":"1992","journal-title":"Arch. Neurol."},{"key":"2026030700084838800_B10","first-page":"L178","article-title":"Antisense oligonucleotides for PDGF-\u03b2 and its receptor inhibit mechanical strain-induced fetal lung cell growth.","volume":"269","author":"Liu","year":"1995","journal-title":"Am. J. Physiol."},{"key":"2026030700084838800_B11"},{"key":"2026030700084838800_B12"},{"key":"2026030700084838800_B13"},{"key":"2026030700084838800_B14","first-page":"367","article-title":"Fetal breathing movements and lung maturation in the congenitally abnormal human fetus.","volume":"6","author":"Dornan","year":"1984","journal-title":"J. Dev. Physiol."},{"key":"2026030700084838800_B15"},{"key":"2026030700084838800_B16","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1159\/000293162","article-title":"Relationship of fetal breathing movement pattern to surfactant phospholipid levels in amniotic fluid and postnatal respiratory complications.","volume":"31","author":"Higuchi","year":"1991","journal-title":"Gynecol. Obstet. Invest."},{"key":"2026030700084838800_B17","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1152\/jappl.1996.81.4.1471","article-title":"Strain-induced growth of the immature lung.","volume":"81","author":"Zhang","year":"1996","journal-title":"J. Appl. Physiol."},{"key":"2026030700084838800_B18","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/S0022-3468(84)80349-8","article-title":"Experimental pulmonary hypoplasia and oligohydramnios: relative contributions of lung fluid and fetal breathing movements.","volume":"19","author":"Adzick","year":"1984","journal-title":"J. Pediatr. Surg."},{"key":"2026030700084838800_B19","first-page":"267","article-title":"The effect of spinal cord transection on lung development in fetal sheep.","volume":"3","author":"Liggins","year":"1981","journal-title":"J. Dev. Physiol."},{"key":"2026030700084838800_B20","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/S0002-9378(97)70440-X","article-title":"The effect of oligohydramnios and cervical cord transection on lung growth in experimental pulmonary hypoplasia in rabbits.","volume":"177","author":"Yoshimura","year":"1997","journal-title":"Am. J. Obstet. Gynecol."},{"key":"2026030700084838800_B21","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1152\/jappl.1975.39.4.513","article-title":"Electrical activity of phrenic nerve and diaphragm in utero.","volume":"39","author":"Bahoric","year":"1975","journal-title":"J. Appl. Physiol."},{"key":"2026030700084838800_B22","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1165\/ajrcmb\/4.4.304","article-title":"Effects of maternal dexamethasone on expression of SP-A, SP-B, and SP-C in the fetal rat lung.","volume":"4","author":"Schellhase","year":"1991","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026030700084838800_B23","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/1654","article-title":"A lungful of transcription factors.","volume":"20","author":"Whitsett","year":"1998","journal-title":"Nature Genetics"},{"key":"2026030700084838800_B24","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1101\/gad.3.5.628","article-title":"Gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program.","volume":"3","author":"Edmondson","year":"1989","journal-title":"Genes Dev."},{"key":"2026030700084838800_B25","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/0092-8674(89)90583-7","article-title":"Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD.","volume":"56","author":"Wright","year":"1989","journal-title":"Cell"},{"key":"2026030700084838800_B26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/gad.8.1.1","article-title":"bHLH factors in muscle development, deadlines and commitments: what to leave in and what to leave out.","volume":"8","author":"Olson","year":"1994","journal-title":"Genes Dev."},{"key":"2026030700084838800_B27","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/364501a0","article-title":"Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene.","volume":"364","author":"Hasty","year":"1993","journal-title":"Nature"},{"key":"2026030700084838800_B28","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/364532a0","article-title":"Myogenin gene disruption results in perinatal lethality because of severe muscle defect.","volume":"364","author":"Nakeshima","year":"1993","journal-title":"Nature"},{"key":"2026030700084838800_B29","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3109\/01902149109064406","article-title":"Lung development in the mouse embryo.","volume":"17","author":"Ten Have-Opbroek, A. A. W","year":"1991","journal-title":"Exp. Lung Res."},{"key":"2026030700084838800_B30","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2535\/ofaj1936.60.1_17","article-title":"Development of the mouse diaphragm.","volume":"60","author":"Jinguji","year":"1983","journal-title":"Okajimas Folia Anatomica Japonica"},{"key":"2026030700084838800_B31","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/0012-1606(84)90127-1","article-title":"Distribution and quantification of ACh receptors and innervation in diaphragm muscle of normal and mdg mouse embryos.","volume":"101","author":"Powell","year":"1984","journal-title":"Dev. Biol."},{"key":"2026030700084838800_B32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0092-8674(00)81073-9","article-title":"Know your neighbors: three phenotypes in null mutants of the myogenic bHLH gene MRF4.","volume":"85","author":"Olson","year":"1996","journal-title":"Cell"},{"key":"2026030700084838800_B33","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/tera.1420330313","article-title":"Pulmonary hypoplasia in chondrodystrophic mice.","volume":"33","author":"Seegmiller","year":"1986","journal-title":"Teratology"},{"key":"2026030700084838800_B34","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/0003-2697(76)90043-9","article-title":"A modified fluorometric method for the determination of microgram quantities of DNA from cell or tissue cultures.","volume":"71","author":"Setaro","year":"1976","journal-title":"Anal. Biochem."},{"key":"2026030700084838800_B35","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1242\/dev.122.6.1693","article-title":"Evidence from normal expression and targeted misexpression that bone morphogenetic protein-4 (BMP-4) plays a role in mouse embryonic lung morphogenesis.","volume":"122","author":"Bellusci","year":"1996","journal-title":"Development"},{"key":"2026030700084838800_B36","first-page":"1323","article-title":"Immunohistochemical determination of in-vivo distribution of Bax, a dominant inhibitor of Bcl-2.","volume":"145","author":"Kraewski","year":"1994","journal-title":"Am. J. Pathol."},{"key":"2026030700084838800_B37","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1083\/jcb.127.1.95","article-title":"Somite, subdomains, muscle cell origins and the four muscle regulatory factor proteins.","volume":"127","author":"Smith","year":"1994","journal-title":"J. Cell Biol."},{"key":"2026030700084838800_B38","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/ar.1092250213","article-title":"Technique for estimating fetal mouse thoracic volume through image analysis of histological sections.","volume":"225","author":"Hepworth","year":"1989","journal-title":"Anat. Rec."},{"key":"2026030700084838800_B39","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/BF00268892","article-title":"Effects of antigen retrieval by microwave heating in formalin-fixed tissue sections on a broad panel of antibodies.","volume":"102","author":"von Waseilewski","year":"1994","journal-title":"Histochem."},{"key":"2026030700084838800_B40","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1083\/jcb.119.3.493","article-title":"Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.","volume":"119","author":"Gavrieli","year":"1992","journal-title":"J. Cell Biol."},{"key":"2026030700084838800_B41","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/(SICI)1097-0177(199703)208:3<398::AID-AJA10>3.0.CO;2-X","article-title":"FGF-1 and FGF-2 induce distinct patterns of growth and differentiation in embryonic lung epithelium.","volume":"208","author":"Cardoso","year":"1997","journal-title":"Dev. Dyn."},{"key":"2026030700084838800_B42","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1165\/ajrcmb.12.5.7742011","article-title":"Retinoic acid induces changes in the pattern of airway branching and alters epithelial cell differentiation in developing lung in vitro.","volume":"12","author":"Cardoso","year":"1995","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026030700084838800_B43","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1242\/dev.119.2.519","article-title":"Expression of the chicken GATA factor family during early erythroid development and differentiation.","volume":"119","author":"Leonard","year":"1993","journal-title":"Development"},{"key":"2026030700084838800_B44"},{"key":"2026030700084838800_B45","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1741-4520.1990.tb00503.x","article-title":"Lung hypoplasia in developing mice and rats induced by maternal exposure to nitrofen.","volume":"30","author":"Ueki","year":"1990","journal-title":"Cong. Anom."},{"key":"2026030700084838800_B46","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1165\/ajrcmb.10.2.7509164","article-title":"Expression of surfactant proteins in embryonic rat lung.","volume":"10","author":"Wang","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026030700084838800_B47","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1002\/ar.1092210409","article-title":"Ultrastructural features of type II alveolar epithelial cells in early embryonic mouse lung.","volume":"221","author":"Ten Have-Opbroek, A. A. W., J. A. Dubbeldam, and C. J. M. Otto-Verberne","year":"1988","journal-title":"Anat. Rec."},{"key":"2026030700084838800_B48","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/(SICI)1097-4547(19960701)45:1<57::AID-JNR5>3.0.CO;2-G","article-title":"Extensive motor neuron survival in the absence of secondary skeletal muscle fiber formation.","volume":"45","author":"Brennan","year":"1996","journal-title":"J. Neurosci. Res."},{"key":"2026030700084838800_B49","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/341303a0","article-title":"Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis.","volume":"3441","author":"Sassoon","year":"1989","journal-title":"Nature"},{"key":"2026030700084838800_B50","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1152\/jappl.1975.39.3.423","article-title":"Diaphragmatic activity and lung liquid flow in the unanesthetized fetal sheep.","volume":"39","author":"Maloney","year":"1975","journal-title":"J. Appl. Physiol."},{"key":"2026030700084838800_B51","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0022-3468(97)90180-9","article-title":"Tracheal ligation increases cell proliferation but decreases surfactant protein in fetal murine lungs in vitro.","volume":"32","author":"Bullard","year":"1997","journal-title":"J. Pediatr. Surg."},{"key":"2026030700084838800_B52","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1146\/annurev.physiol.59.1.575","article-title":"Tensegrity: the architectural basis of cellular mechanotransduction.","volume":"59","author":"Ingber","year":"1997","journal-title":"Annu. Rev. Physiol."},{"key":"2026030700084838800_B53","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1165\/ajrcmb.18.1.2744","article-title":"Apoptosis in the development of rat and human fetal lungs.","volume":"18","author":"Scavo","year":"1998","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026030700084838800_B54"},{"key":"2026030700084838800_B55","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1101\/gad.13.2.213","article-title":"p21CIP1 and p57KIP2 control muscle differentiation at the myogenin step.","volume":"13","author":"Zhang","year":"1999","journal-title":"Genes Dev."},{"key":"2026030700084838800_B56"},{"key":"2026030700084838800_B57","first-page":"47","article-title":"Fetal lung growth in laryngeal atresia and tracheal agenesis.","volume":"25","author":"Scurry","year":"1989","journal-title":"Aust. Paeditr. J."}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/22\/3\/304\/67191887\/ajrcmb_22_3_304.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/22\/3\/304\/67191887\/ajrcmb_22_3_304.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T05:19:52Z","timestamp":1772860792000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/22\/3\/304\/8502828"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,3,1]]},"references-count":57,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2000,3,1]]},"published-print":{"date-parts":[[2000,3,1]]}},"URL":"https:\/\/doi.org\/10.1165\/ajrcmb.22.3.3708","relation":{},"ISSN":["1535-4989","1044-1549"],"issn-type":[{"value":"1535-4989","type":"electronic"},{"value":"1044-1549","type":"print"}],"subject":[],"published-other":{"date-parts":[[2000,3]]},"published":{"date-parts":[[2000,3,1]]}}}