Developmental abnormalities in mice transgenic for bovine oncostatin M

Area of Science:

• Biochemistry
• Molecular Biology
• Immunology

Background:

• Oncostatin M is a hematopoietin cytokine binding a gp130 receptor complex.
• The evolutionary conservation of Oncostatin M has remained largely uncharacterized.
• Only the human form of Oncostatin M has been previously identified.

Purpose of the Study:

• To isolate and characterize a nonprimate Oncostatin M gene.
• To investigate the in vitro and in vivo functions of bovine Oncostatin M.
• To explore the evolutionary conservation and pleiotropic effects of Oncostatin M.

Main Methods:

• Isolation of a bovine gene encoding a protein 58% identical to human Oncostatin M.
• In vitro assays demonstrating bovine Oncostatin M binding to human cells and inhibiting tumor/leukemia cell proliferation.
• In vivo studies involving transgenic mice with tissue-specific expression of bovine Oncostatin M fusion genes.

Main Results:

• Bovine Oncostatin M shares structural similarities with human Oncostatin M, including a four-alpha-helical-bundle structure.
• Bovine Oncostatin M exhibits conserved biological activities, inhibiting proliferation of human and mouse cancer cell lines.
• In vivo, overexpression of bovine Oncostatin M led to reduced transgenic mouse frequencies and developmental abnormalities, including issues with bone growth, spermatogenesis, pancreatic fibrosis, and lymphoid tissue.

Conclusions:

• This study establishes the existence of a nonprimate Oncostatin M gene.
• Bovine Oncostatin M demonstrates pleiotropic functions in vivo, impacting multiple developmental processes.
• Understanding bovine Oncostatin M can contribute to characterizing this cytokine's structure and function in other vertebrates.