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Gene Review

Crlf2  -  cytokine receptor-like factor 2

Mus musculus

Synonyms: CRLM-2, CRLM2, Crlm2, Cytokine receptor-like factor 2, Cytokine receptor-like molecule 2, ...
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Disease relevance of Tpte2

  • The incidence of gallstones decreased from 90% in control mice to 33% in Mttp(Delta/Delta) mice after 8 weeks of a lithogenic diet (P < .0001) [1].
  • Unlike the "conventional" LTalpha-/- mice, new LTalphaDelta/Delta animals were capable of producing normal levels of systemic TNF upon lipopolysaccharide (LPS) challenge and were susceptible to LPS/D-galactosamine (D-GalN) toxicity [2].
  • In C57BL/6 adult female mice, ICP47-defective virus (Delta ICP47, F strain) was less able to invade the organs studied than was wild-type HSV-1 F strain, showing that ICP47 influences general invasiveness [3].

High impact information on Tpte2

  • Lfng-null progenitors generated few thymocytes in competitive assays, whereas Lfng overexpression converted thymocytes into 'supercompetitors' with enhanced binding of Delta-like ligands and blocked T lymphopoiesis from normal progenitors [4].
  • Furthermore, TSLPR KO mice fail to develop an inflammatory lung response to inhaled antigen unless supplemented with wild-type CD4+ T cells [5].
  • Additionally, CD4(+) T cells from TSLPR KO mice expanded less efficiently than WT CD4(+) T cells in irradiated hosts, and TSLP preferentially expanded CD4(+) T cells both in vitro and in vivo [6].
  • Moreover, sublethally irradiated TSLPR KO mice showed weaker recovery of lymphocyte populations than wild-type (WT) littermates, even when neutralizing anti-IL-7 antibodies were injected [6].
  • Thus, the functional TSLPR requires the IL-7Ralpha chain, but not the gammac chain for signaling [7].

Biological context of Tpte2

  • Transfection of TSLPR cDNA resulted in only low affinity binding [7].
  • The murine CRLM-2 gene is composed of 8 exons, and an alternative mRNA splicing generates a variant transcript encoding a soluble CRLM-2 [8].
  • The phenotype of the new LTalphaDelta/Delta mice indicates that LTalpha plays a smaller role in lymphoid organ maintenance than previously thought and has no direct role in the regulation of TNF expression [2].

Anatomical context of Tpte2

  • These data strongly suggest that CRLM-2 is a novel cytokine receptor involved in the regulation of hematopoietic system [8].
  • CRLM-2 is preferentially expressed in hematopoietic cells, particularly in hematopoietic progenitors and myeloid cells [8].
  • Notch signaling plays a pivotal role in the differentiation of hair cells and supporting cells by mediating lateral inhibition via the ligands Delta-like 1 and Jagged (JAG) 2 [9].
  • The mechanism of the protective effect appears to be increased biliary phospholipid output in Mttp(Delta/Delta) mice, leading to significant unsaturation of gallbladder bile [1].
  • Additionally, we observed a mild myeloid expansion and decrease in mature B cells within the Rb(Delta/Delta) bone marrow but a similar contribution to phenotypic HSC populations compared with nondeleted bone marrow [10].

Associations of Tpte2 with chemical compounds

  • Furthermore, CRLM-2 is constitutively associated with JAK2, a well-known tyrosine kinase that transmits signals from cytokine receptors [8].
  • We exploited Cre-LoxP technology to generate a novel neomycin resistance gene (neo) cassette-free LTalpha-deficient mouse strain (neo-free LTalpha KO [LTalphaDelta/Delta]) [2].
  • METHODS: Allergen-dependent airway inflammation and hyperresponsiveness was induced in conditional alpha4(Delta/Delta), VCAM-1(-/-), and beta2(-/-) mice [11].

Analytical, diagnostic and therapeutic context of Tpte2

  • Molecular cloning and characterization of CRLM-2, a novel type I cytokine receptor preferentially expressed in hematopoietic cells [8].
  • Both immunoblotting and ELISA with recombinant mouse TSLPR/Fc chimera as antigen, having only the N-terminal domain of mTSLPR present, indicated that the generated monoclonal antibodies identify the C-terminus of mTSLPR [12].


  1. Inactivation of hepatic microsomal triglyceride transfer protein protects mice from diet-induced gallstones. Amigo, L., Castro, J., Miquel, J.F., Zanlungo, S., Young, S., Nervi, F. Gastroenterology (2006) [Pubmed]
  2. Novel lymphotoxin alpha (LTalpha) knockout mice with unperturbed tumor necrosis factor expression: reassessing LTalpha biological functions. Liepinsh, D.J., Grivennikov, S.I., Klarmann, K.D., Lagarkova, M.A., Drutskaya, M.S., Lockett, S.J., Tessarollo, L., McAuliffe, M., Keller, J.R., Kuprash, D.V., Nedospasov, S.A. Mol. Cell. Biol. (2006) [Pubmed]
  3. ICP47 mediates viral neuroinvasiveness by induction of TAP protein following intravenous inoculation of herpes simplex virus type 1 in mice. Burgos, J.S., Serrano-Saiz, E., Sastre, I., Valdivieso, F. J. Neurovirol. (2006) [Pubmed]
  4. Regulation of T lymphopoiesis by Notch1 and Lunatic fringe-mediated competition for intrathymic niches. Visan, I., Tan, J.B., Yuan, J.S., Harper, J.A., Koch, U., Guidos, C.J. Nat. Immunol. (2006) [Pubmed]
  5. A role for TSLP in the development of inflammation in an asthma model. Al-Shami, A., Spolski, R., Kelly, J., Keane-Myers, A., Leonard, W.J. J. Exp. Med. (2005) [Pubmed]
  6. A role for thymic stromal lymphopoietin in CD4(+) T cell development. Al-Shami, A., Spolski, R., Kelly, J., Fry, T., Schwartzberg, P.L., Pandey, A., Mackall, C.L., Leonard, W.J. J. Exp. Med. (2004) [Pubmed]
  7. Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: Formation of a functional heteromeric complex requires interleukin 7 receptor. Park, L.S., Martin, U., Garka, K., Gliniak, B., Di Santo, J.P., Muller, W., Largaespada, D.A., Copeland, N.G., Jenkins, N.A., Farr, A.G., Ziegler, S.F., Morrissey, P.J., Paxton, R., Sims, J.E. J. Exp. Med. (2000) [Pubmed]
  8. Molecular cloning and characterization of CRLM-2, a novel type I cytokine receptor preferentially expressed in hematopoietic cells. Hiroyama, T., Iwama, A., Morita, Y., Nakamura, Y., Shibuya, A., Nakauchi, H. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  9. The Notch ligand JAG1 is required for sensory progenitor development in the mammalian inner ear. Kiernan, A.E., Xu, J., Gridley, T. PLoS Genet. (2006) [Pubmed]
  10. Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells. Walkley, C.R., Orkin, S.H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. alpha4 and beta2 integrins have nonredundant roles for asthma development, but for optimal allergen sensitization only alpha4 is critical. Banerjee, E.R., Jiang, Y., Henderson, W.R., Scott, L.M., Papayannopoulou, T. Exp. Hematol. (2007) [Pubmed]
  12. Soluble thymic stromal lymphopoietin receptors are absent in murine sera--detection with anti-mTSLPR monoclonal antibodies. Rosenqvist, L., Andersson, A.M., Ohls, S., Boström, M., Nordström, T., Lindqvist, C. APMIS (2005) [Pubmed]
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