Microarray analysis of Myf5-/-:MyoD-/- hypoplastic mouse lungs reveals a profile of genes involved in pneumocyte differentiation

M. Baguma-Nibasheka, H.E. Angka, M.R. Inanlou and B. Kablar

Dalhousie University, Faculty of Medicine, Department of Anatomy and Neurobiology, Halifax, NS, Canada

Offprint requests to: Boris Kablar, Dalhousie University, Faculty of Medicine, Department of Anatomy and Neurobiology, 5850 College Street, Halifax NS, Canada B3H 1X5. e-mail: bkablar@dal.ca


Summary. Fetal breathing-like movements (FBMs) are important in normal lung growth and pneumocyte differentiation. In amyogenic mouse embryos (designated as Myf5-/-:MyoD-/-, entirely lacking skeletal musculature and FBMs), type II pneumocytes fail to differentiate into type I pneumocytes, the cells responsible for gas exchange, and the fetuses die from asphyxia at birth. Using oligonucleotide microarrays, we compared gene expression in the lungs of Myf5-/-:MyoD-/- embryos to that in normal lungs at term. Nine genes were found to be up-regulated and 54 down-regulated at least 2-fold in the lungs of double-mutant embryos. Since many down-regulated genes are involved in lymphocyte function, immunohistochemistry was employed to study T- and B-cell maturity in the thymus and spleen. Our findings of normal lymphocyte maturity implied that the down-regulation was specific to the double-mutant lung phenotype and not to its immune system. Immunostaining also revealed altered distribution of transcription and growth factors (SATB1, c-Myb, CTGF) from down-regulated genes whose knockouts are now known to undergo embryonic or neonatal death secondary to respiratory failure. Together, it appears that microarray analysis has identified a profile of genes potentially involved in pneumocyte differentiation and therefore in the mechanisms that may be implicated in the mechanochemical signal transduction pathways underlying FBMs-dependent pulmonary hypoplasia. Histol Histopathol 22, 483-495 (2007)

Key words: Pneumocyte differentiation, Pulmonary hypoplasia, Mouse embryo, Myf5 and MyoD, cDNA microarray

DOI: 10.14670/HH-22.483