Disease relevance of Re

• This mutation exhibits corneal opacity as well as abnormal skin and hair development resembling rex denuded (Re(den)) and bareskin (Bsk) [1].
• Later, the denuded areas developed a keratosis which was prone to infection [2].
• To investigate the nature of this protection, dogs and rabbits were immunized with purified glycolipid prepared by phenol-chloroform-petroleum ether extraction of the "Re" mutant of Salmonella minnesota 595 and opsonophagocytic and bactericidal tests were carried out using lapine peritoneal granulocytes and serum factors [3].
• Results from receptor-binding assays conducted with B16 F1 murine melanoma cells indicated that receptor-binding affinity was reduced to approximately 1% of its original levels after Re incorporation into the cyclic Cys4,10, D-Phe7-alpha-MSH4-13 analog [4].
• In all of the in vitro assays, these synthetic compounds exhibited high activities comparable to those of a reference lipid A prepared from Escherichia coli O8:K27 Re-mutant strain F515 [5].

High impact information on Re

• Unlike secondary oocytes, fertilized eggs denuded of their zona pellucida no longer contained the enzyme, suggesting that tissue-type PA production stops at or around fertilization, and that the bulk of the enzyme is secreted at this time [6].
• The locus at which the denuded blastocysts attached to the culture dish was usually a random section of their mural trophoblasts, in which case single egg cylinders developed unilaterally [7].
• By electron microscopy both strains showed a similar attachment of PMN to the denuded GBM together with swelling and necrosis of endothelial cells [8].
• Furthermore, markers of leukocyte activation - in particular, increased expression of the beta2-integrin Mac-1 (alphaMbeta2, or CD11b/CD18), which is responsible for firm leukocyte adhesion to platelets and fibrinogen on denuded vessels - predict restenosis after PTCA [9].
• The injury destroyed all medial smooth muscle cells, denuded the injured segment of intact endothelium, and induced transient platelet-rich mural thrombosis [10].

Chemical compound and disease context of Re

• In these studies we utilized intrinsically labeled 14C-labeled LPS from Salmonella minnesota or the 14C-labeled glycolipid derived from the Re mutant of S. minnesota (R595) [11].
• Monophosphoryl lipid A (MPL) from Salmonella typhimurium Re mutant strain was used as a potential immune response modifier in some vaccines [12].
• Treatment with nontoxic monophosphoryl lipid A (MPL) derived from a polysaccharide-deficient, heptoseless Re mutant of either Salmonella typhimurium or Salmonella minnesota R595 enhanced the immunoglobulin M (IgM) anti-type III pneumococcal polysaccharide (SSS-III) antibody response of C3H/HeSnJ mice [13].
• Lipopolysaccharide (LPS) extracted from three strains of Salmonella typhimurium, i.e., the rough Re mutant SL1102, the rough Ra mutant TV119, and the smooth strain SH4809, was first electrodialyzed (eLPS) and then divalent cation deprived by EDTA treatment and finally made monomeric by deoxycholate solubilization [14].
• Immunotherapeutic agents studied included live Bacillus Calmette-Guerin (BCG) preparations in varying doses and strains (Tice, Pasteur, and Glaxo), Re mutant glycolipid (ReG) from Salmonella typhimurium, BCG cell wall skeletons (CWS), CWS plus B4 glycolipid fraction of ReG, and Keyhole-Limpet Hemocyanin (KLH) [15].

Biological context of Re

• The dominant alopecia phenotypes Bareskin, Rex-denuded, and Reduced Coat 2 are caused by mutations in gasdermin 3 [16].
• The Hox-2 homeo box gene complex on mouse chromosome 11 is closely linked to Re [17].
• A single copy fragment was isolated from the 3' flanking region of the U1a1 gene and used as a hybridization probe for Southern blotted DNAs from recombinant inbred strains of mice, mouse-hamster hybrid cells, and the offspring from backcrosses between BALB/c mice and mice which were heterozygous for the Rex (Re) marker [18].
• Characterization and mapping of DNA sequence homologous to mouse U1a1 snRNA: localization on chromosome 11 near the Dlb-1 and Re loci [18].
• Redesign of the metal binding site resulted in a second-generation Re-peptide complex (ReCCMSH) that displayed a receptor-binding affinity of 2.9 nM, 25-fold higher than the initial Re-alpha-MSH analog [4].

Anatomical context of Re

• Therefore, the endogenous C1q of macrophages also appears to be involved in attachment of the S. minnesota Re mutant [19].
• In contrast to the S-form of Salmonella minnesota, its Re mutant binds to mouse peritoneal macrophages [19].
• Macrophages preincubated with immunoglobulin G-sensitized erythrocytes had a low chemiluminescent signal, and after treatment of the cells with the Re mutant, there was an additional, higher signal [19].
• In vitro stimulation of spleen cells from animals classically immunized with Salmonella Re mutant enhanced the number of lipid A-specific IgG-producing hybridomas from six after direct fusion to 17 after stimulation [20].
• Salmonella Re mutants are non-invasive for cell monolayers but still can enter and replicate in L-929 murine fibroblast cells [21].

Associations of Re with chemical compounds

• IgM antibody to the Re mutant was protective against bacterial challenge with both test strains of bacteria and S. typhi LPS [22].
• Spermidine concentration in the livers of both male and female PRO/Re mice was approx. 130% that of the controls [23].
• Male PRO/Re mice excreted putrescine at 175% and spermidine at 300% the amount of male C57BL/6J controls [23].
• The increased polyamine biosynthesis and excretion in the PRO/Re mutant mice may be a mechanism to decrease the extent of proline accumulation [23].
• When the concentrations of the polyamines in the tissues of the PRO/Re mice were determined, spermidine and spermine concentrations in the kidneys of the male PRO/Re mice were twice those of the controls [23].

Regulatory relationships of Re

• There was no significant difference between PRO/Re and C57BL/6J male mice for either putrescine- or spermidine-stimulated S-adenosylmethionine decarboxylase activity [23].
• SMC forming a pseudoendothelium in chronically denuded vessels continued to express high levels of VCAM-1 and MCP-1, thus perpetuating the inflammatory response [24].
• Müllerian inhibiting substance (MIS) inhibited the resumption of meiosis in both denuded and cumulus cell-enclosed rat oocytes in vitro [25].

Other interactions of Re

• A family of type I keratin genes and the homeobox-2 gene complex are closely linked to the rex locus on mouse chromosome 11 [26].
• Examination of the enzymes involved in polyamine biosynthesis revealed that ornithine decarboxylase, the initial enzyme in the polyamine-biosynthetic pathway, was increased by 150% in the kidneys and by 100% in the liver of male PRO/Re mice [23].
• Preincubation of macrophages with the Re mutant abolishes immunoglobulin G-sensitized erythrocyte-induced chemiluminescence [19].
• Mouse protection induced by Pseudomonas aeruginosa PAC1R and its defective mutants, Salmonella minnesota Re-mutant and Escherichia coli O14 [27].
• The animals challenged with WT LPS showed a decrease in uterine cAMP when the mice were starting to expel the fetuses while the Re LPS treated group maintained control levels of cAMP [28].

Analytical, diagnostic and therapeutic context of Re

• Active and passive immunization with Re chemotype mutants of Salmonella minnesota afforded significant protection against heterologous gram-negative bacilli and were considerably more effective than immunization with smooth S. minnesota or its Ra, Rb, Rc, Rd1 and Rd2 mutants [29].
• Mouse monoclonal antibodies were raised against heat-killed bacteria of the Re mutant R595 of Salmonella minnesota and characterized by the passive hemolysis and passive hemolysis inhibition tests and by double immunodiffusion experiments using lipopolysaccharide (LPS) from different rough mutants of S. minnesota and synthetic antigens [30].
• Active immunization experiments were also performed with the Re mutant of Salmonella minnesota 595 which carries a lipopolysaccharide composed of lipid A and three residues of ketodeoxyoctonic acid [31].
• Membrane proteins of the murine-pre-B-cell line 70Z/3 were separated by SDS-PAGE, transferred electrophoretically onto nitrocellulose, and the blot was incubated with LPS of the Salmonella minnesota Re-mutant R595 (mRe-LPS) [32].
• Transmission electron microscopy, light microscopy, and immunohistochemistry revealed that electric injury destroyed all medial smooth muscle cells, denuded the injured segment of intact endothelium, and transiently induced platelet-rich mural thrombosis [33].

References