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Gene Review

Lim2  -  lens intrinsic membrane protein 2

Mus musculus

Synonyms: 19kDa, 4833403J20, Lens fiber membrane intrinsic protein, MP17, MP18, ...
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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


  1. Refractive defects and cataracts in mice lacking lens intrinsic membrane protein-2. Shiels, A., King, J.M., Mackay, D.S., Bassnett, S. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  2. Myeloid commitment shifts toward monocytopoiesis after thermal injury and sepsis. Santangelo, S., Gamelli, R.L., Shankar, R. Ann. Surg. (2001) [Pubmed]
  3. Bone marrow cellular composition in Listeria monocytogenes infected mice detected using ER-MP12 and ER-MP20 antibodies: a flow cytometric alternative to differential counting. de Bruijn, M.F., van Vianen, W., Ploemacher, R.E., Bakker-Woudenberg, I.A., Campbell, P.A., van Ewijk, W., Leenen, P.J. J. Immunol. Methods (1998) [Pubmed]
  4. CpG oligodeoxynucleotide enhances immunity against blood-stage malaria infection in mice parenterally immunized with a yeast-expressed 19 kDa carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (MSP1(19)) formulated in oil-based Montanides. Hirunpetcharat, C., Wipasa, J., Sakkhachornphop, S., Nitkumhan, T., Zheng, Y.Z., Pichyangkul, S., Krieg, A.M., Walsh, D.S., Heppner, D.G., Good, M.F. Vaccine (2003) [Pubmed]
  5. Nitric oxide induces BNIP3 expression that causes cell death in macrophages. Yook, Y.H., Kang, K.H., Maeng, O., Kim, T.R., Lee, J.O., Kang, K.I., Kim, Y.S., Paik, S.G., Lee, H. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  6. Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Bronte, V., Apolloni, E., Cabrelle, A., Ronca, R., Serafini, P., Zamboni, P., Restifo, N.P., Zanovello, P. Blood (2000) [Pubmed]
  7. Identification of hematopoietic stem cell subsets on the basis of their primitiveness using antibody ER-MP12. van der Loo, J.C., Slieker, W.A., Kieboom, D., Ploemacher, R.E. Blood (1995) [Pubmed]
  8. Characterization of murine hematopoietic progenitor subsets involved in interleukin-3-induced interleukin-6 production. Schneider, E., Ploemacher, R.E., Navarro, S., van Beurden, C., Dy, M. Blood (1991) [Pubmed]
  9. Cyclophosphamide induces the development of early myeloid cells suppressing tumor cell growth by a nitric oxide-dependent mechanism. Peláez, B., Campillo, J.A., López-Asenjo, J.A., Subiza, J.L. J. Immunol. (2001) [Pubmed]
  10. Temporal expression of three mouse lens fiber cell membrane protein genes during early development. Zhou, L., Chen, T., Church, R.L. Mol. Vis. (2002) [Pubmed]
  11. 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. Zhou, L., Li, X., Church, R.L. Mol. Vis. (2001) [Pubmed]
  12. Identification of a mutation in the MP19 gene, Lim2, in the cataractous mouse mutant To3. Steele, E.C., Kerscher, S., Lyon, M.F., Glenister, P.H., Favor, J., Wang, J., Church, R.L. Mol. Vis. (1997) [Pubmed]
  13. Two new cataract loci, Ccw and To3, and further mapping of the Npp and Opj cataracts in the mouse. Kerscher, S., Glenister, P.H., Favor, J., Lyon, M.F. Genomics (1996) [Pubmed]
  14. Lim2(To3) transgenic mice establish a causative relationship between the mutation identified in the lim2 gene and cataractogenesis in the To3 mouse mutant. Steele, E.C., Wang, J.H., Lo, W.K., Saperstein, D.A., Li, X., Church, R.L. Mol. Vis. (2000) [Pubmed]
  15. Repopulation of murine Kupffer cells after intravenous administration of liposome-encapsulated dichloromethylene diphosphonate. Yamamoto, T., Naito, M., Moriyama, H., Umezu, H., Matsuo, H., Kiwada, H., Arakawa, M. Am. J. Pathol. (1996) [Pubmed]
  16. Does lens intrinsic membrane protein MP19 contain a membrane-targeting signal? Chen, T., Li, X., Yang, Y., Erdene, A.G., Church, R.L. Mol. Vis. (2003) [Pubmed]
  17. Characterization of the ovine-lens plasma-membrane protein-kinase substrates. Arneson, M.L., Cheng, H.L., Louis, C.F. Eur. J. Biochem. (1995) [Pubmed]
  18. Generation of a conditionally immortalized myeloid progenitor cell line requiring the presence of both interleukin-3 and stem cell factor to survive and proliferate. Lee, C., Evans, C.A., Spooncer, E., Pierce, A., Mottram, R., Whetton, A.D. Br. J. Haematol. (2003) [Pubmed]
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