Genes that modify expression of major urinary proteins in mice.

Duncan, R; Matthai, R; Hüppi, Konrad; Roderick, T; Potter, Michael

doi:10.1128/mcb.8.7.2705

Cited by 19 publications

(10 citation statements)

References 15 publications

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“…Variation in Mup protein levels is observed in different strains of mice (29). This difference is most pronounced in BALB/cJ mice, which express Mups at considerably lower levels than what is seen in other strains, including other BALB/c substrains (30). This reduced Mup expression in BALB/cJ mice was mapped to a locus on mouse chromosome 15 (30).…”

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confidence: 94%

“…This difference is most pronounced in BALB/cJ mice, which express Mups at considerably lower levels than what is seen in other strains, including other BALB/c substrains (30). This reduced Mup expression in BALB/cJ mice was mapped to a locus on mouse chromosome 15 (30). The dramatic reduction in urinary Mup levels in BALB/cJ mice led us to investigate whether this trait was due to the Zhx2 mutation.…”

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confidence: 95%

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Zhx2 (zinc fingers and homeoboxes 2) regulates major urinary protein gene expression in the mouse liver

Jiang

Creasy

Purnell

et al. 2017

Journal of Biological Chemistry

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The mouse major urinary proteins (Mups) are encoded by a large family of highly related genes clustered on chromosome 4. Mups, synthesized primarily and abundantly in the liver and secreted through the kidneys, exhibit male-biased expression. Mups bind a variety of volatile ligands; these ligands, and Mup proteins themselves, influence numerous behavioral traits. Although urinary Mup protein levels vary between inbred mouse strains, this difference is most pronounced in BALB/cJ mice, which have dramatically low urinary Mup levels; this BALB/cJ trait had been mapped to a locus on chromosome 15. We previously identified Zhx2 (zinc fingers and homeoboxes 2) as a regulator of numerous liver-enriched genes. is located on chromosome 15, and a natural hypomorphic mutation in the BALB/cJ allele dramatically reduces Zhx2 expression. Based on these data, we hypothesized that reduced Zhx2 levels are responsible for lower Mup expression in BALB/cJ mice. Using both transgenic and knock-out mice along with assays, our data show that Zhx2 binds Mup promoters and is required for high levels of Mup expression in the adult liver. In contrast to previously identified Zhx2 targets that appear to be repressed by Zhx2, Mup genes are positively regulated by Zhx2. These data identify Zhx2 as a novel regulator of Mup expression and indicate that Zhx2 activates as well as represses expression of target genes.

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confidence: 94%

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confidence: 95%

Zhx2 (zinc fingers and homeoboxes 2) regulates major urinary protein gene expression in the mouse liver

Jiang

Creasy

Purnell

et al. 2017

Journal of Biological Chemistry

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“…Structurally, MUPs have molecular weights of about 19 kD and acidic isoelectric points in the range of 4.2 to 4.7 (Duncan et al 1988). A 2.4 Å crystal structure for MUP‐I isolated from mouse urine (Böcskei et al 1992) confirmed that MUPs are members of the lipocalin family of protein structures characterized by a conserved β‐barrel structure consisting of eight β‐strands and an α‐helix (for review, see Flower 1996).…”

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confidence: 99%

Structural basis of pheromone binding to mouse major urinary protein (MUP‐I)

et al. 2001

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The mouse major urinary proteins are pheromone-binding proteins that function as carriers of volatile effectors of mouse physiology and behavior. Crystal structures of recombinant mouse major urinary protein-I (MUP-I) complexed with the synthetic pheromones, 2-sec-butyl-4,5-dihydrothiazole and 6-hydroxy-6-methyl-3-heptanone, have been determined at high resolution. The purification of MUP-I from mouse liver and a high-resolution structure of the natural isolate are also reported. These results show the binding of 6-hydroxy-6-methyl-3-heptanone to MUP-I, unambiguously define ligand orientations for two pheromones within the MUP-I binding site, and suggest how different chemical classes of pheromones can be accommodated within the MUP-I ␤-barrel.

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“…19 kDa. They are encoded by a multigene family which is differentially expressed in a number of secretory tissues [1–3], and the synthesis of these proteins, found only in the urine of sexually mature male mice, is under multihormonal control [4,5]. Thus, not surprisingly, urine turns out to be one of the main sources of olfactory chemosignals for mice, controlling for example sexual attraction among conspecifics, mating and puberty acceleration [6–8].…”

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Solution structure of a recombinant mouse major urinary protein

Lücke

Franzoni

Abbate

et al. 1999

European Journal of Biochemistry

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Major urinary proteins (MUPs) form an ensemble of protein isoforms which are expressed and secreted by sexually mature male mice only. They belong to the lipocalin superfamily and share with other members of this family the capacity to bind hydrophobic molecules, some of which are odorants. MUPs, either associated with or free of their natural ligands, play an important role in the reproductive cycle of these rodents by acting as pheromones. In fact, they are able to interact with receptors in the vomeronasal organ of the female mice, inducing hormonal and physiological responses by an as yet unknown mechanism.In order to investigate the structural and dynamical features of these proteins in solution, one of the various wild-type isoforms (rMUP: 162 residues) was cloned and subsequently isotopically labeled. The complete 1 H, 13C and 15 N resonance assignment of that isoform, achieved by using a variety of multidimensional heteronuclear NMR experiments, has been reported recently.Here, we describe the refined high-resolution three-dimensional solution structure of rMUP in the native state, obtained by a combination of distance geometry and energy minimization calculations based on 2362 NOE-derived distance restraints. A comparison with the crystal structure of the wild-type MUPs reveals, aside from minor differences, a close resemblance in both secondary structure and overall topology.The secondary structure of the protein consists of eight antiparallel b-strands forming a single b-sheet and an a-helix in the C-terminal region. In addition, there are several helical and hairpin turns distributed throughout the protein sequence, mostly connecting the b-strands. The tertiary fold of the b-sheet creates a b-barrel, common to all members of the lipocalin superfamily. The shape of the b-barrel resembles a calyx, lined inside by mostly hydrophobic residues that are instrumental for the binding and transport of small nonpolar ligand molecules.Keywords: heteronuclear NMR spectroscopy; isotope enrichment [ 15 N, 13 C]; lipocalin; major urinary protein; pheromones.The mouse major urinary proteins (MUPs) comprise an ensemble of acidic protein isoforms with a molecular mass of approx. 19 kDa. They are encoded by a multigene family which is differentially expressed in a number of secretory tissues [1±3], and the synthesis of these proteins, found only in the urine of sexually mature male mice, is under multihormonal control [4,5]. Thus, not surprisingly, urine turns out to be one of the main sources of olfactory chemosignals for mice, controlling for example sexual attraction among conspecifics, mating and puberty acceleration [6±8].From a structural point of view, MUPs belong to the lipocalin superfamily [9±11], a large and rapidly increasing family of extracellular proteins characterized by the ability to bind small hydrophobic molecules. Despite a rather low similarity in the primary sequence, they have been shown to possess a highly conserved three-dimensional fold featuring an a-helix located in the C-terminal region an...

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Genes that modify expression of major urinary proteins in mice.

Cited by 19 publications

References 15 publications

Zhx2 (zinc fingers and homeoboxes 2) regulates major urinary protein gene expression in the mouse liver

Zhx2 (zinc fingers and homeoboxes 2) regulates major urinary protein gene expression in the mouse liver

Structural basis of pheromone binding to mouse major urinary protein (MUP‐I)

Solution structure of a recombinant mouse major urinary protein

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