Disease relevance of Mip

• Bilateral congenital cataracts result from a gain-of-function mutation in the gene for aquaporin-0 in mice [1].
• The Mip-like protein of Chlamydia trachomatis has sequence similarity with both the Mip protein of Legionella pneumophila, a virulence factor necessary for optimal intracellular infection, and FK506-binding proteins (FKBPs) of both prokaryotic and eukaryotic origin [2].
• Chlamydia trachomatis Mip-like protein has peptidyl-prolyl cis/trans isomerase activity that is inhibited by FK506 and rapamycin and is implicated in initiation of chlamydial infection [2].
• Cysteine protease activated by expression of HIV-1 protease in transgenic mice. MIP26 (aquaporin-0) cleavage and cataract formation in vivo and ex vivo [3].
• Mycobacterial phagosomes acquired Cat D, although strains BCG and H37Rv phagosomes contained the inactive 46-kDa form, whereas H37Ra phagosomes had the active 30-kDa form [4].

High impact information on Mip

• With respect to morphological and molecular differentiation, alpha A/L-myc lenses were characterized by a severely disorganized lens fiber cell compartment and a significant decrease in the expression of a late-stage differentiation marker (MIP26); in contrast, differentiation appeared to be unaffected in alpha A/c-myc mice [5].
• Scanning electron microscopy further revealed that mature fiber cells within the core of the heterozygous CatFr lens failed to stratify into uniform, concentric growth shells, suggesting that the AQP0 water channel facilitates the development of the unique cellular architecture of the crystalline lens [6].
• Here we show that disruption of the AQP0 gene by an early transposon (ETn) element results in expression of a chimeric protein, comprised of approximately 75% AQP0 and approximately 25% ETn long terminal repeat (LTR) sequence, in the cataract Fraser (CatFr) mouse lens [6].
• Coincident with active Cat D, H37Ra-infected macrophages presented the epitope to T cells inducing IL-2, whereas H37Rv- and BCG-infected macrophages were less efficient in IL-2 induction [4].
• Furthermore, the small interfering RNA interference of Cat D synthesis resulted in a marked decrease in the levels of macrophage-induced IL-2 [4].

Biological context of Mip

• Freeze-fracture and fracture labeling revealed that the junctional assembly, packing organization and topographic interactions between connexons and MP26 differed when Cx46 and Cx50 were co-assembled in the wild-type or expressed separately in the two distinct knockout phenotypes [7].
• The Hfi locus was mapped to the distal part of mouse chromosome 10 close to the major intrinsic protein (Mip), which is expressed only in cell membranes of lens fibers [8].
• Hfi is a dominant cataract mutation where heterozygotes show hydropic lens fibers and homozygotes show total lens opacity [8].
• Sequence analysis of Aqp0 revealed a 12-bp deletion without any change in the reading frame, which resulted in a deletion of four amino acids within the second transmembrane region of the AQP0 protein [1].
• Targeted expression of the mutated Aqp0 caused lens opacity in transgenic mice, the pathological severity of which depended on the expression level of the transgene [1].

Anatomical context of Mip

• If the lens is maturing, mutations affecting the lens membranes (aquaporins/Mip, Lim-2 or connexins) or the structural proteins of the cytosol of the lens fiber cells (the crystallins) become more important [9].
• Mice deficient in the gene for AQP0 (Aqp0, Mip) were generated from a library of gene trap embryo stem cells [10].
• The cAMP-dependent protein-kinase-catalyzed phosphorylation of the two major intrinsic lens fiber cell plasma membrane proteins, MP20 and MP26, is likely restricted to the inner cortical and nuclear regions of the lens in vivo [11].
• Lentoid and monolayer cultures of each cell line were examined for transcripts of the lens-specific alpha A-crystallin ("alpha A"), gamma D-crystallin ("gamma D"; formerly gamma 1-crystallin) and MP26 genes. alpha TN4 lentoid bodies contained 2.5 times the alpha A RNA found in monolayer cells, but lacked detectable gamma D and MP26 RNA [12].
• Optical dysfunction of the crystalline lens in aquaporin-0-deficient mice [10].

Associations of Mip with chemical compounds

• Organ culture of transgenic lenses with E64, a cysteine protease inhibitor, dramatically delayed cataractogenesis and prevented proteolytic cleavage of both MIP26 and crystallins [3].
• However, in addition to GPX4, we detected a second major protein of 26 kDa (MP26) that was eluted from purified hamster sperm tails by the disulfide-reducing agent dithiothreitol [13].
• Phenytoin (PHT) is metabolized primarily to 5-(4-hydroxyphenyl)-5-phenylhydantoin (4-HPPH), a 3,4-dihydrodiol metabolite (DHD), and a catechol, 5-(3,4-dihydroxyphenyl)-5-phenylhydantoin (Cat) [14].
• Alterations of urea-insoluble membrane fraction, MP26, of Emory mouse lenses in aging and cataractogenesis [15].
• Aquaporin 0 (AQP0) is the major intrinsic protein of the lens and its water permeability can be modulated by changes in pH and Ca(2+) [16].

Other interactions of Mip

• Two genes involved in lens development and differentiation, Pax6 and MIP26 were also misexpressed [17].
• Specific interaction between lens MIP/Aquaporin-0 and two members of the gamma-crystallin family [18].
• In mice, the models include the Cts strain, Fraser mouse, lens opacity gene (Lop) strain, Lop-2 and Lop-3 strains, Philly mouse, Nakano mouse, Nop strain, Deer mouse, Emory mouse, Swiss Webster strain, Balb/c-nct/nct mouse, and SAM-R/3 strain [19].
• Alterations to the internal lens hydration state also occur; therefore, the status of the aquaporin protein MIP26 was examined over postnatal days 16-25 to determine if it was altered during cataractogenesis [3].

Analytical, diagnostic and therapeutic context of Mip

• METHODS: The expression profile of Palm protein in the embryonic, newborn and adult mouse eye as well as dissociated retinal neurons was determined by confocal immunofluorescence [20].
• Macrophages were infected with GFP-expressing mycobacterial strains and analyzed for in situ localization of vacuolar proton ATPase (v-ATPase) and cathepsin D (Cat D) using Western blot analysis and immunofluorescence [4].
• Indirect immunofluorescence localized MP26 to the midpiece, and two-dimensional PAGE and immunoblot analysis identified a single MP26 isoform of pI 9 [13].
• Male Crj:CD-1 mice (3 wk old) were fed a diet containing 2% DHA and 3% palm oil (DHA group); 5% PC (PC group); 1% DHA, 2.5% PC and 1.5% palm oil (DHA + PC group); 5% palm oil (Palm oil control group) or MF laboratory chow (MF control group) for 7 mo [21].

References