Respiratory Distress and Early Neonatal Lethality in Hspa4l/Hspa4 Double-Mutant Mice
Copyright policy )Respiratory Distress and Early Neonatal Lethality in Hspa4l/Hspa4 Double-Mutant Mice
Heat shock proteins HSPA4L and HSPA4 are closely related members of the HSP110 family and act as cochaperones. We generated Hspa4l(-/-)Hspa4(-/-) mice to investigate a functional complementarity between HSPA4L and HSPA4 during embryonic development. Hspa4l(-/-)Hspa4(-/-) embryos exhibited marked pulmonary hypoplasia and neonatal death. Compared with lungs of wild-type, Hspa4l(-/-), and Hspa4(-/-) embryos, Hspa4l(-/-)Hspa4(-/-) 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(-/-)Hspa4l(-/-) 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(-/-)Hspa4(-/-) lungs. Further experiments showed a significant accumulation of ubiquitinated proteins in the lungs of Hspa4l(-/-)Hspa4(-/-) 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.
- University of Göttingen Germany
- National Research Centre Egypt
- Hannover Medical School Germany
Lung Diseases, Mice, Knockout, Respiratory Distress Syndrome, Newborn, Mice, 129 Strain, Genotype, Respiration, Gene Expression Regulation, Developmental, Apoptosis, Epithelial Cells, Gestational Age, Mice, Inbred C57BL, Mice, Phenotype, Morphogenesis, Animals, Abnormalities, Multiple, HSP70 Heat-Shock Proteins, HSP110 Heat-Shock Proteins, Lung, Cell Proliferation
Lung Diseases, Mice, Knockout, Respiratory Distress Syndrome, Newborn, Mice, 129 Strain, Genotype, Respiration, Gene Expression Regulation, Developmental, Apoptosis, Epithelial Cells, Gestational Age, Mice, Inbred C57BL, Mice, Phenotype, Morphogenesis, Animals, Abnormalities, Multiple, HSP70 Heat-Shock Proteins, HSP110 Heat-Shock Proteins, Lung, Cell Proliferation
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).13 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!