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Mouse major urinary proteins (MUPs) are encoded by a family of about 35 to 40 highly conserved genes. In the preceding paper (K. Shahan, M. Gilmartin, and E. Derman, Mol. Cell. Biol. 7:1938-1946, 1987, we presented the sequences of the most abundant MUP mRNAs in the liver (MUP I, II, and III) and in the lachrymal (MUP IV) and submaxillary (MUP V) glands. We have shown that these five mRNAs are coded by five distinct genes, MUP I through V. In the present communication, we examine the expression of MUP genes in all of the six tissues in which MUP mRNAs are synthesized, the mammary, parotid, sublingual, lachrymal, and submaxillary glands and the liver. We show that gene MUP II is expressed in the liver and in the mammary gland, that gene MUP IV is expressed in the lachrymal and parotid glands, and that gene MUP V is expressed in the submaxillary, sublingual, and lachrymal glands. Furthermore, we present evidence that in addition to genes MUP I through V, another gene, MUP VI, is expressed in BALB/c mice in the parotid gland. The tissue-specific synthesis of MUP mRNAs is thus brought about by two major mechanisms: the expression, in different tissues, of different members of the family and the expression of a single gene at various levels in different tissues. When a particular MUP gene is expressed in several tissues, transcripts of this gene initiate at the same site and are spliced and polyadenylated in the same manner.The mouse major urinary proteins (MUPs) are secretory proteins encoded by a family of genes that exhibit sequence conservation of at least 85%, both in the transcribed and in the flanking sequences (4; Y. Shi and E. Derman, unpublished data). MUPs are synthesized in six different tissues: the liver and the lachrymal, submaxillary, parotid, sublingual, and mammary glands (14, 16). In the liver, MUPs are synthesized in response to several hormones such as testosterone, growth hormone, glucocorticoid hormones, and thyroxine and only in post-pubescent mice (10, 16). In contrast, in the submaxillary and lachrymal glands, MUPs are synthesized in prepubescent mice as well as in adult mice (16). The hormonal regulation in these two glands, however, does vary. Whereas the synthesis of MUPs in the submaxillary gland does not appear to be hormonally controlled, the synthesis of the lachrymal gland MUPs is regulated by testosterone (16).In the preceding paper (15), we described the sequences of the major species of MUP mRNAs in the liver and in the lachrymal and submaxillary glands, MUP I, II, III, IV, and V. These five mRNAs are encoded by five distinct members of the MUP gene family. The focus of the studies presented here is to examine the synthesis of MUP mRNAs in three additional tissues, the mammary, parotid, and sublingual glands, and to define the expression of each of the previously identified genes, MUPI to V. To this end, we characterized the expression of individual MUP genes with the synthetic oligonucleotide probes described in the preceding paper (15), in male and in female mice and at various ...

The mouse major urinary proteins (MUPs) are encoded by a gene family of about 35 to 40 members. MUPs are synthesized in at least six secretory tissues under a variety of developmental and endocrine controls, but the identities of the individual genes expressed in each tissue have not previously been established. In this article, we present the nucleotide sequences of five MUP mRNAs which we designate MUP I through V. MUPs I, H, and III are the most abundant MUP mRNA species in the liver, and MUPs IV and V are the most abundant MUP mRNA species in the lachrymal gland and the submaxillary gland, respectively. The sequence data show that each of the five mRNAs is encoded by a distinct member of the gene family. The structures of the MUP mRNA consist of interspersed segments of variable and conserved sequences. On the basis of the sequences of the variable segments, gene-specific panels of synthetic oligonucleotide probes were prepared. The gene-specific panels were used to identify cloned genes and, as described in the accompanying paper (K. Shahan, M. Denaro, M. Gilmartin, Y. Shi, and E. Derman, Mol. Cell. Biol. 7:1947Biol. 7: -1954Biol. 7: , 1987, to characterize the expression of MUP genes I through V.

The nucleoside analog 5, 6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB) at 75 to 150 micromolar concentrations inhibits the synthesis of nuclear heterogeneous RNA (hnRNA) in HeLa cells by 60 to 70 percent. The sedimentation profile of hnRNA labeled with (3H)uridine for 45 seconds after brief treatment (45, 90, or 180 seconds) with DRB showed a progressive decrease in the labeling of shorter hnRNA molecules relative to longer molecules. Prior exposure of the cells to actinomycin D, an inhibitor of RNA chain elongation, did not alter the sedimentation profile of hnRNA. These results suggest that DRB preferentially inhibits the initiation of hnRNA chains so that after exposure to DRB for a brief period the longer nascent chains still remain to be finished and thus incorporate a greater share of the pulse label. By progressively increasing the time of exposure to DRB, and measuring the rate of increase in the average size of the labeled, nascent RNA, it was estimated that the chains were growing at rates between 50 and 100 nucleotides per second.

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