Respiratory Distress and Early Neonatal Lethality in Hspa4l/Hspa4 Double-Mutant Mice
2014 | journal article. A publication with affiliation to the University of Göttingen.
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Respiratory Distress and Early Neonatal Lethality in Hspa4l/Hspa4 Double-Mutant Mice
Mohamed, B. A.; Barakat, A. Z.; Held, T.; Elkenani, M.; Muehlfeld, C.; Maenner, J. & Adham, I. M. (2014)
American Journal of Respiratory Cell and Molecular Biology, 50(4) pp. 817-824. DOI: https://doi.org/10.1165/rcmb.2013-0132OC
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Details
- Authors
- Mohamed, Belal A.; Barakat, Amal Z.; Held, Torsten; Elkenani, Manar; Muehlfeld, Christian; Maenner, Joerg; Adham, Ibrahim M.
- Abstract
- Heat shock proteins HSPA4L and HSPA4 are closely related members of the HSP110 family and act as cochaperones. We generated Hspa4l(-1-) Hspa4(-1-) mice to investigate a functional complementarity between HSPA4L and HSPA4 during embryonic development. Hspa4l(-1-) Hspa4(-1-) 2 embryos exhibited marked pulmonary hypoplasia and neonatal death. Compared with lungs of wild- type, Hspa4l(-1-) , and Hspa4(-1-) embryos, Hspa4l(-1-) Hspa4(-1-) lungs were characterized by diminished saccular spaces and increased mesenchymal septa. Mesenchymal hypercellularity was determined to be due to an increased cell proliferation index and decreased cell death. A significant increase in expression levels of prosurvival protein B cell leukemia/ lymphoma 2 may be the cause for inhibition of apoptotic process in lungs of Hspa4(-1-) Hspa4l(-1-) embryos. Accumulation of glycogen and diminished expression of surfactant protein B, prosurfactant protein C, and aquaporin 5 in saccular epithelium suggested impaired maturation of type II and type I pneumocytes in the Hspa4l(-1-) Hspa4(-1-) lungs. Further experiments showed a significant accumulation of ubiquitinated proteins in the lungs of Hspa4l(-1-) Hspa4(-1-) embryos, indicating an impaired chaperone activity. Our study demonstrates that HSPA4L and HSPA4 collaborate in embryonic lung maturation, which is necessary for adaptation to air breathing at birth.
- Issue Date
- 2014
- Status
- published
- Publisher
- Amer Thoracic Soc
- Journal
- American Journal of Respiratory Cell and Molecular Biology
- ISSN
- 1535-4989; 1044-1549