Disease relevance of Lim2

• Heterozygous Lim2 gene-trap lenses (Lim2(Gt/+)) were morphologically indistinguishable from wild type, whereas homozygous Lim2 gene-trap lenses (Lim2(Gt/Gt)) consistently developed faint, central pulverulent cataracts [1].
• Flow cytometric analysis of early (ER-MP12) and late (ER-MP20) monocyte progenitors showed an increase in monocyte lineage growth in burn sepsis [2].
• Bone marrow cellular composition in Listeria monocytogenes infected mice detected using ER-MP12 and ER-MP20 antibodies: a flow cytometric alternative to differential counting [3].
• The 19kDa carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (MSP1(19)), an analog of the leading falciparum malaria vaccine candidate, induces protective immunity to challenge infection when formulated with complete/incomplete Freund's adjuvant (CFA/IFA), an adjuvant unsuitable for use in humans [4].
• In this report, we used cDNA microarray analysis to show that SNAP, an NO donor, strongly induces Bcl-2/adenovirus E1B 19kDa-interacting protein 3 (BNIP3) in macrophages [5].

High impact information on Lim2

• We isolated iMacs from the spleens of immunocompromised mice and found that these cells were positive for CD31, ER-MP20 (Ly-6C), and ER-MP58, markers characteristic of granulocyte/monocyte precursors [6].
• When used in two-color immunofluorescence with ER-MP20 (anti-Ly-6C), six subpopulations of bone marrow (BM) cells could be identified [7].
• In addition, erythroblasts, granulocytes, lymphocytes, and monocytes could almost be fully separated on the basis of ER-MP12 and ER-MP20 antigen expression [7].
• Indeed, the Rh-dull population that is enriched for cells with marrow repopulating activity does not respond to the growth factor and mature cells cannot be induced to express IL-6 as assessed by (1) FLS/PLS characteristics, (2) the monoclonal antibody ER-MP 20 recognizing monocytes and granulocytic cells, and (3) in situ hybridization [8].
• Cy-treated mice develop splenic early myeloid (CD11b, Gr-1, CD31 (ER-MP12), ER-MP20, ER-MP54) cells producing large amounts of NO upon T cell-derived signals (IFN-gamma plus CD40 ligation) able to inhibit tumor cell growth in vitro [9].

Biological context of Lim2

• CONCLUSIONS: The identified early expression of Cx50, MIP, and Lim2 transcripts in mouse embryonic stages suggests that all three proteins play very important, probably quite different, roles in lens fiber cell differentiation [10].
• The size of mouse Lim2 is 5,896 base pairs from the transcriptional start site to the poly(A) signal, and contains five exons and four introns [11].
• The aim of this study was to screen the Lim2 gene in the To3 mutant for a genetic lesion that was correlated and consistent with the mutant phenotype [12].
• Exons 2-5 of the Lim2 gene encode a polypeptide of 173 amino acids, having over 92% identity to human MP19 [11].
• Total opacity 3, To3, maps to Chromosome 7, 7.1 +/- 1.8 cM proximal to p (pink-eyed dilution) [13].

Anatomical context of Lim2

• From this screening, an 11 kb genomic fragment was isolated which contained the entire Lim2 gene, and a neighboring gene, Nkg7, which codes for a 17 kDa granulocyte membrane protein termed GMP-17 [11].
• METHODS: Lim2-deficient mice were derived from a library of gene-trap embryo stem cells [1].
• PURPOSE: To characterize the optical properties of lenses from mice deficient in the gene for lens intrinsic membrane protein-2 (Lim2), which encodes the second most abundant integral protein (Lim2) of lens fiber cell plasma membranes [1].
• CONCLUSIONS: These data show that heterozygous loss of Lim2 is insufficient to trigger cataracts in mice, and they provide the first direct evidence that Lim2 plays a critical role in establishing the correct internal refractive properties of the crystalline lens [1].
• The murine Lim2 promoter was characterized by transfecting primary chicken lens epithelial cells with Lim2 promoter-CAT reporter constructs and assaying promoter activity and specificity [14].

Associations of Lim2 with chemical compounds

• This DNA change results in the nonconservative substitution of a valine for the normally encoded glycine at amino acid 15 of the MP19 polypeptide [12].
• The numbers of macrophage precursors in the liver as detected by the monoclonal antibodies ER-MP20 and ER-MP58 increased after liposome-entrapped dichloromethylene diphosphonate injection [15].
• In contrast, when EGFP/MP19 (with EGFP fused to the NH2-terminal end of intact MP19, GMP19) was expressed, the fusion protein did integrate into the cell membrane, identical to MP19G [16].

Other interactions of Lim2

• RESULTS: An 11,182 base pair genomic clone containing the entire murine Lim2 gene and another downstream gene, Nkg7, was obtained and completely sequenced [11].
• 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 [17].
• IL-3- and SCF-dependent clonal cell lines were derived with a phenotype (lin-, Sca-1+, CD34+, ER-MP 58+, ER-MP 12+, ER-MP 20-) characteristic of primitive myeloid progenitors [18].

Analytical, diagnostic and therapeutic context of Lim2

• PCR was used to generate overlapping fragments of the entire Lim2 gene from these DNAs [12].
• The mouse lens fiber-cell intrinsic membrane protein MP19 gene (Lim2) and granule membrane protein GMP-17 gene (Nkg7): Isolation and sequence analysis of two neighboring genes [11].
• Lim2 expression was analyzed by reverse transcription (RT)-PCR and Northern blotting of lens total RNA, immunoblotting of lens membrane extracts, and immunofluorescence confocal microscopy of lens sections [1].
• RT-PCR analysis revealed a very low ratio of Lim2To3 transgenic mRNA compared to endogenous normal Lim2 [14].
• As an alternative, we have examined whether double labelling of bone marrow with the anti-precursor monoclonal antibodies ER-MP12 and ER-MP20 could be used for differential analysis by flow cytometry, as these antibodies define six relatively homogeneous cell populations in mouse bone marrow [3].

References