A 45-kb DNA domain with two divergently orientated genes is the unit of organisation of the murine major urinary protein genes.

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sequence conservation of at least 85%, both in the transcribed and in the flanking sequences (4; Y. Shi and E. Derman, unpublished data).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 group 2 genes have consequently been considered to be pseudogenes. It has been shown that the group 1 and group 2 genes are arranged in head-to-head-oriented gene pairs (5).…”

Section: Resultsmentioning

confidence: 99%

Expression of six mouse major urinary protein genes in the mammary, parotid, sublingual, submaxillary, and lachrymal glands and in the liver.

Shahan¹,

Denaro²,

Gilmartin³

et al. 1987

“…The MUPs are encoded by a multigene family estimated to contain approximately 30 genes per haploid genome (3,12). The structural genes are organized in a tandem array on chromosome 4 (6). Utilizing a MUP cDNA probe and Southern hybridization, Bennett et al (2) reported a restriction fragment length polymorphism (RFLP) among inbred strains.…”

mentioning

confidence: 99%

Genes that modify expression of major urinary proteins in mice.

Duncan¹,

Matthai²,

Hüppi³

et al. 1988

A survey of major urinary proteins (MUPs) from eight BALB/c mouse substrains by isoelectric focusing identified a common pattern with about 10 protein bands in males. One substrain, BALB/cJPt, differed The major urinary proteins (MUPs) of the mouse are a group of 19,000-molecular-weight, structurally and antigenically related proteins with isoelectric points (pls) in the range of pH 4.2 to 4.7. MUPs are synthesized predominantly in the liver but also in salivary, mammary, and other secretary glands. The MUPs produced in the liver are secreted into the plasma and excreted through the kidneys into the urine (9). Normal males excrete 5 to 20 times as much MUP as females. Gonadectomy reduces the quantity of MUP excreted by males to the female level (10). Administration of testosterone induced females and castrated males to excrete levels of MUP characteristic of normal males, indicating the regulatory role of this hormone.A genetic locus originally designated Mup-a (now called

“…The average divergence within exons from the group 1 consensus sequence is only 0.35% (6,17). A high degree of homology between group 1 genes within introns and 3 to 4 kilobases (kb) of 5' and 3' flanking sequences has also been inferred by cross hybridization and restriction enzyme site mapping (4,9).…”

mentioning

confidence: 98%

“…Two-dimensional polyacrylamide gel electrophoresis of MUP liver mRNA in vitro translation products or urinary protein from C57BL/6J mice indicates that several MUP genes expressed in male liver are not expressed in female liver (15,17). Based on sequence homology, MUP genes can be grouped into two major subfamilies, group 1 and group 2, each consisting of approximately 15 genes (4,5,9). A third group * Corresponding author.…”

mentioning

confidence: 99%

Identification and characterization of functional genes encoding the mouse major urinary proteins.

Held¹,

Gallagher²,

Hohman³

et al. 1987

Mouse Ltk-cells were stably transfected with cloned genes encoding the mouse major urinary proteins (MUPs). C57BL/6J MUP genomic clones encoding MUP 2 (BL6-25 and BL6-51), MUP 3 (BL6-11 and BL6-3), and MUP 4 (BL6-42) have been identified. In C57BL/6J mice, MUP 2 and MUP 4 are known to be synthesized in male, but not female, liver, and MUP 3 is known to be synthesized in both male and female liver and mammary gland. A BALB/c genomic clone (BJ-31) was shown to encode a MUP that is slightly more basic than MUP 2 and was previously shown to be synthesized in both male and female liver of BALB/c but not C57BL/6 mice. Comigration on two-dimensional polyacrylamide gels of the MUPs encoded by the transfecting gene provides a basis for tentative identification of the tissue specificity and mode of regulation of each gene. DNA sequence analysis of the 5' flanking region indicates that the different MUP genes are highly homologous (0.20 to 2.40% divergence) within the 879 base pairs analyzed. The most prominent differences in sequence occur within an A-rich region just 5' of the TATA box. This region (from -47 to -93) contains primarily A or C(A)N nucleotides and varies from 15 to 46 nucleotides in length in the different clones.