Disease relevance of Mup4

• The bGH analogue produced by the M4 mice resulted in a doubling (P < 0.001) of body weight in comparison with the NTC mice, a result of the increasing (P < 0.001) rate of weight gain [1].
• The M4 receptors seem to play a modest role in salivation, but did not alter hypothermia and tremor [2].
• In the M2 knockout mice, agonist-induced bradycardia in isolated spontaneously beating atria was completely absent compared to their wild type litter mates, whereas agonist-induced bradycardia was similar in the M4 knockout and wild type mice [2].

High impact information on Mup4

• 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 [3].
• 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 [3].
• In this M4 line, thyroid dysgenesis leading to growth retardation and premature death was observed upon serial backcross that enhanced the DBA/2J genetic background [4].
• The development of thyroid tumors in M1, M2, M4 transgenic mice demonstrates the oncogenic potential of activated Ras gene in the thyroid gland [4].
• The M4 gene of gammaHV68 encodes a secreted glycoprotein and is required for the efficient establishment of splenic latency [5].

Biological context of Mup4

• Three lines of transgenic mice expressing mutant bovine growth hormone (bGH) genes and displaying small (G119K), near normal (M11) or large (M4) phenotypes and nontransgenic control (NTC) mice were used to determine GH-associated, age-specific changes in empty body composition [1].
• The M4 line raises interesting questions relative to the interference between the Ras-mediated signal transduction pathway and thyroid morphogenesis [4].
• Here, we show that one of these ORFs, M4, encodes a secreted glycoprotein that influences the establishment of splenic latency at early times post-infection [5].
• The deduced amino acid sequence of the M4 peptide included two unique repetitive sequences of amino acids and a conserved sequence motif which is found in several proteins including the CS protein (region II) [6].

Anatomical context of Mup4

• The potency of carbachol to stimulate contraction of isolated stomach fundus, urinary bladder and trachea was reduced by a factor of about 2 in the M2 knockout mice, but was unaltered in the M4 knockout mice [2].
• The binding of the muscarinic agonist, [3H]-oxotremorine-M, was reduced in cortical tissue from the M2 knockout mice and to a lesser extent from the M4 knockout mice, and was reduced over 90% in the brain stem of M2 knockout mice [2].
• Muscarine did not excite nociceptors in the wild-type littermates (WT) and M4 knock-out (M4 KO) mice, but almost all fibers exhibited marked desensitization to mechanical and heat stimuli [7].
• These results suggest that M4 mediates an extracellular host-pathogen interaction that impacts the establishment of latent infection in the spleen, but not the peritoneum [5].
• By in vitro transcription of equivalent cDNA clones, translation of the resulting RNA in the reticulocyte lysate system and isoelectric focusing, the protein products of genes BL1, BS1 and BS6 were shown to be MUP 2a, MUP 2b and MUP 4 respectively [8].

Associations of Mup4 with chemical compounds

• (-)-5-(3',4',5'-Trihydroxyphenyl)-gamma-valerolactone (M4) and (-)-5-(3',4'-dihydroxyphenyl)-gamma-valerolactone (M6), the ring-fission metabolites of EGC and (-)-epicatechin, respectively, were also predominantly in monoglucuronide and monosulfate forms in the urine [9].

Other interactions of Mup4

• By polymerase chain reaction, we identified two cDNA segments encoding MUP 4 and MUP 5 genes in the nose [10].

References