Am. J. Respir. Cell Mol. Biol.,
Volume 22, Number 3, March, 2000 304-315
Pulmonary Hypoplasia in the myogenin Null Mouse Embryo
Brian S.
Tseng,*
Sash T.
Cavin,
Frank W.
Booth,
Eric N.
Olson,
Maria Carmen
Marin,**
Timothy J.
McDonnell,
and
Ian J.
Butler
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
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'-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.
*
Current address: Brian S. Tseng, M.D., Ph.D., Department of Pediatrics,
University of Colorado, The Children's Hospital, 1056 East 19th Street,
Denver, CO 80218.
**
Current address: Maria Carmen Marin, Ph.D., Dana-Farber Cancer Institute, 44 Binney St. Mayer 452, Boston, MA 02115.
