Introduction of the human pro alpha 1(I) collagen gene into pro alpha 1(I)-deficient Mov-13 mouse cells leads to formation of functional mouse-human hybrid type I collagen.

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Abstract
The Mov-13 mouse stain carriers a retroviral insertion in the pro.alpha.(I) collagen gene that prevents transcription of the gene. Cell lines derived from homozygous embryos do not express type I collagen although normal amounts of pro.alpha.2 mRNA are synthesized. We have introduced genomic clones of either the human or mouse pro.alpha.1(I) collagen gene into homozygous cell lines to assess whether the human or mouse pro.alpha.1(I) chains can associate with the endogenous mouse pro.alpha.2(I) chain to form stable type I collagen. The human gene under control of the simian virus 40 promoter was efficiently transcribed in the transfected cells. Protein analyses revealed that stable heterotrimers consisting of two human .alpha.1 chains and one mouse .alpha.2 chain were formed and that type I collagen was secreted by the transfected cells at normal rates. However, the electrophoretic migration of both .alpha.1(I) and .alpha.2(I) chains in the human-mouse hybrid molecules were retarded, compared to the .alpha.(I) chains in control mouse cells. Inhibition of the posttranslational hydroxylation of lysine and proline resulted in comigration of human and mouse .alpha.1 and .alpha.2 chains, suggesting that increased posttranslational modification caused the altered electrophoretic migration in the human-mouse hybrid molecules. Amino acid sequence differences between the mouse and human .alpha. chains may interfere with the normal rate of helix formation and increase the degree of posttranslational modifications similar to those observed in patients with lethal perinatal osteogenesis imperfecta. The Mov-13 mouse system should allow us to study the effect specific mutations introduced in transfected pro.alpha.1(I) genes have on the synthesis, assembly, and function of collagen I.