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The mdx mouse is an animal model for Duchenne muscular dystrophy (DMD), which is caused by the absence of dystrophin. Mdx limb muscles substantially compensate for the lack of dystrophin while the diaphragm is affected like DMD skeletal muscles. To understand better the complex cascade of molecular events leading to muscle degeneration and compensatory processes in mdx muscles, we analyzed alterations of gene expression in mdx hindlimb and diaphragm muscles as compared to their normal counterparts. The strategy was based on suppression subtractive hybridization followed by reverse Northern quantitative hybridization. Four subtracted/normalized libraries, containing cDNA clones up- or downregulated in mdx hindlimb muscles or diaphragm, were constructed and a total of 1536 cDNA clones were analyzed. Ninety-three cDNAs were found to be differentially expressed in mdx hindlimb muscles and/or diaphragm. They corresponded to 54 known genes and 39 novel cDNAs. The potential role of the known genes is discussed in the context of the mdx phenotype.

Rat hepatocytes have the potential to secrete three similar acidic glycoproteins, serine protease inhibitors 1, 2 and 3 (SPI-1, SPI-2, SPI-3), recognized by the same antibodies. They were synthesized as precursors of comparable sizes (45 kDa), which were post-translationally modified by N-glycosylation at three (SPI-3) or four (SPI-1 and SPI-2) sites. This appeared to account for the size difference of mature proteins. The mRNA sequences, derived from cDNA clones, displayed a high degree of similarity (70-90%), except the sequence of the antiproteasereactive centers which were completely divergent. SPI-1 and SPI-2 mRNAs were of similar sizes (1.8 kb), and were smaller than that of SPI-3 (2.2 kb); the difference corresponded to a longer, 3'-end untranslated sequence. Production of SPI-1 and SPI-2, which was constitutive in the normal animal, could be abolished by hypophysectomy and was strongly decreased during acute inflammation. In contrast, production of SPI-3, which was barely detectable in normal rats, was transiently induced during inflammation.The family of serine proteinase inhibitors, referred to as serpins (for a review, see [l]), appears to display, from a functional point of view, a great deal of diversity. While many members of this continuously growing family (e. g. cc,-antitrypsin, ccl-antichymotrypsin, antithrombin 111, serine proteinase inhibitors, a,-antiplasmin, plasminogen activator inhibitor 1 and horse leukocyte elastase inhibitor) have the wellestablished property of inhibiting serine proteases by forming irreversible complexes in a 1 : 1 molar ratio with proteinases [2], several others are not proteinase inhibitors. This subclass includes precursors of biologically active peptides such as angiotensinogen [3,4], carrier proteins like thyroxine-binding protein [5] and corticosteroid-binding globulin 161, and proteins like ovalbumin [7] and the barley protein Z [S], which do not possess any well-defined function. Another interesting feature of the serpins is the fact that a variety of factors have been shown to control the expression of their genes. Thus, genes encoding ovalbumin and related proteins are regulated by steroid hormones [9], those encoding antiproteases that belong to the group of acute-phase proteins [lo, 111 are under the control of glucocorticoids and inflammatory cytokines (for a review, see [12]) and the gene encoding the plasminogen activator inhibitor type 1 is regulated by various effectors including hormones and growth factors (for a review, see 1131). Serine proteinase inhibitors (SPI), secreted by rat liver, represent a remarkable example of the aforementioned feature. Rat hepatocytes have been shown to secrete proteins Correspondence to A.

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