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A genetic locus closely linked to a protease inhibitor gene complex controls the level of multiple RNA transcripts

Hill, Robert E. and Shaw, Phillip H. and Barth, Richard K. and Hastie, Nicholas D. (1985) A genetic locus closely linked to a protease inhibitor gene complex controls the level of multiple RNA transcripts. Molecular and Cellular Biology, 5 (8). pp. 2114-2122. ISSN 0270-7306.

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The two major protease inhibitors in mouse plasma are alpha 1-protease inhibitor (alpha 1-PI), putative inhibitor of neutrophil elastase, and contrapsin, an inhibitor in vitro of trypsinlike proteases. We have shown by nucleotide sequence analysis that these two inhibitors are related (R. E. Hill, P. H. Shaw, P. A. Boyd, H. Baumann, and N. D. Hastie, Nature (London) 311:175-177, 1984). Here, we show that the contrapsin and alpha 1-PI genes are members of two different multigene families, each containing at least three genes in mice and rats. We established the chromosomal locations of these genes by analyzing the segregation of restriction fragment length polymorphisms in recombinant inbred mouse strains. These experiments show that the multiple genes in each family are clustered and that the two gene families are closely linked on chromosome 12. Thus the genes for contrapsin and alpha 1-PI are likely to have evolved by duplication of a common ancestral gene. The contrapsin multigene family codes for multiple mRNA transcripts in the liver. There is a genetic difference among inbred mouse strains in the regulation of two of these transcripts. In some inbred strains the transcripts are synthesized constitutively; in others they are induced by inflammation. We mapped in recombinant inbred strains the regulatory locus responsible for this genetic variation and found it is linked to the contrapsin multigene family, which suggests a cis-acting regulatory element. We also found that the contrapsin and the alpha 1-PI multigene families have acquired very different regulatory responses since the time of the gene duplication event.

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Additional Information:Copyright © 1985 by the American Society for Microbiology. Received 11 February 1985/Accepted 21 May 1985 We thank Benjamin Taylor for the computer analysis of the RI strains, Bill Held for the use of the fractionated reticulocyte lysate translation system, and Frank Berger for many of the RNA preparations. We also thank Mary Bodis for expert technical assistance, Richard Meehan for critical advice, Katie Rae for excellent assistance in the preparation of the manuscript, and Norman Davidson, Douglas Stuart, and Sandy Bruce for expert photographic work.
Issue or Number:8
Record Number:CaltechAUTHORS:HILmcb85
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2263
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Deposited On:20 Mar 2006
Last Modified:02 Oct 2019 22:51

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