| First Author | Wilson SD | Year | 1989 |
| Journal | Mouse News Lett | Volume | 85 |
| Pages | 14-16 | Mgi Jnum | J:20639 |
| Mgi Id | MGI:68717 | Citation | Wilson SD, et al. (1989) Localization of five cytokine genes to Chromosome 11. Mouse News Lett 85:14-16 |
| abstractText | Full text of MNL contribution: Research News: Localization of Five Cytokine Genes to Chromosome 11. The presence of positionally conserved amino acid residues suggests that the mouse proteins TCA3, P500, MIPl-alpha, MIP1-beta, and JE are encoded by a single gene family (1,2). These proteins are activation-specific and can be expressed by both myeloid and lymphoid cells. MIPl-alpha, MIP1-beta, and MCAF (the putative human homologue of JE) act as chemotactic and activating agents on neutrophils or macrophages (3,4). The functions of TCA3 and P500 are unknown (although preliminary data suggest that TCA3 has proinflammatory properties). We have used interspecies somatic cell hybrids and recombinant inbred mouse strains to map the genes encoding TCA3, MIPl-alpha, MIPl-beta, and JE (provisionally termed Tca-3, Mip-lalpha, Mip-lbeta, and Sigje, respectively) to a cluster on the distal portion of mouse chromosome 11 near the Hox-2 gene complex. DNA sequence analysis indicates that the P500 and TCA3 proteins are encoded by alternative splicing products of one genomic gene. The genes encoding TCA3 and JE show striking similarities in the predicted positions of intron-exon boundaries. Together, these data support the model that the cytokines TCA3, P500, MIPI-alpha, MIP1-beta, and JE are encoded by a single cluster of related genes. Southern blots containing PvuII-digested genomic DNA from four rat-mouse microcell hybrid cell lines were screened with the cDNA probes for Tca-3, Mip-la, Mip-lb, and Sigje as well as Il-5, Csfm and Il-7. Two of these cell lines (F(11)U and F(11)J) had received a single intact chromosome, chromosome 11, from the mouse parent cell line (5). The other two cell lines (FB(11)U and FB(11)J) represent chromosome 11 segregants derived from F(l l)U and F(11)J respectively (5). cDNA probes for Tca-3, Mip-la, Mip-lb, Sigje, and Il-5 all hybridized to a band or bands identical to the mouse (C57BL/6) pattern in the chromosome 11-positive hybrids F(11)U and F(11)J. These bands were absent from the chromosome 11 segregants (lacking chromosome 11) FB(11)U and FB(11)J as well as from the rat parent line FTO-2B, No hybridization corresponding to the mouse patterns was detected in any of the rat-mouse hybrids for Il-7 or Csfm. These results demonstrated that the genes Tca-3, Mip-1a, Mip-1b, Sigje, and Il-5 are contained on mouse chromosome 11. The Il-7 and Csfm genes apparently do not lie on this chromosome. Southern blot analysis of genomic DNA digested with each of a panel of restriction enzymes revealed restriction fragment length variants associated with each gene among the strains 020/A, STS/A, BALB/cJ, AKR/J, C57BL/6J, C57L/J and DBA2/J. The strain distribution patterns (SDPÕs) of the variants were determined for all informative OXA, AKXL, CXS, and BXD recombinant inbred (RI) strains of mice (table 1). Mip-1a and Mip-1b yielded identical SDPÕs among 44 informative RI strains, indicating at 95% confidence that the two genes are less than 2.3 cM apart. The one recombinant between these genes and Tca-3 indicates a distance of 0.6 cM (95% confidence limits of 0.02 Ð 3.7 cM). In turn, the one recombinant among 18 AKXL strains informative for Tca-3 and Evi-2 and the five recombinants among 32 AKXL and CXS strains informative for Tca-3 and Hox-2 suggest a location for the complex on chromosome 11 approximately 5 cM proximal to the Hox-2 gene complex. The SDP data for JE by themselves (two of 14 strains recombinant between Sigje and Tca-3) do not allow conclusions to be drawn as to linkage. However, when the BAYLOC algorithm (6) was applied to these data, using the assignment of JE to chromosome 11 from somatic cell hybrid data to reduce the effective genome size for the computation to 150 cM, Sigje showed linkage to Tca-3 at 95% confidence. The gene encoding interleukin-5, which acts as a T cell replacing factor, a B cell growth factor, and an eosinophil differentiation factor, was also mapped to using RI lines. The SDP for Il-5 was scored in the BXD, OXA, and CXS strains of mice (table 1). Il-5 did not show close linkage to Tca-3, Mip-1a, Mip-1b, or Sigje (21/54), 11/26, and 6/14 discordant, respectively). However, Il-5 showed tight linkage with Il-4 and Il-3 (0/28 and 1/28 discordant respectively). Based on the data obtained from the BXD RI strains, Il-5 is also tightly linked (0/26 discordant) to the gene D4S10h and is located approximately 25 centimorgans proximal to the Tca-3 cluster on chromosome 11. References 1). Wolpe, S.D. and Cerami, A. (1989) FASEB J. In Press. 2). Burd, P.R., Rollins, B.J., Wilson, S.D., Billings, P.R., Stiles, C.D., and Dorf, M.E. (1988) Cell. Immunol. 115, 481-483. 3). Wolpe, S.D., Davatelis, G., Sherry, B., Beutler, B., Hesse, D.G., Nguyen, H.T., Moldawer, L.L., Nathan, C.F., Lowry, S.F., and Cerami, A. (1988) J. Exp. Med. 167, 570-581. 4). Furutani, Y., Nomura, H., Notake, M., Oyamada, Y., Fukui, T., Yamada, M., Larsen, C., Oppenheim, J.J., and Matsushima, K. (1989) Biochem. Biophys. Res. Corm. 159, 249-255. 5). Killary, A.M. and Fournier, R.E.K. (1984) Cell 38, 523-534. 6). Blank, R.D., Campbell, G.R., Calabro, A., and D'Eustachio, P. (1988) Genetics 120, 1073-1083. Table 1: RI strain distribution patterns for 5 cytokine genes located on chromosome 11 Locus: Tca-3; RI Set: BXD: 1: B; 2: D; 5: D; 6: B; 8: B; 9: D; 11: B; 12: D; 13: B; 14: D; 15: D; 16: D; 18: B; 19: D; 20: D; 21: D; 22: D; 23: B; 24: B; 25: B; 27: B; 28: B; 29: D; 30: B; 31: B; 32: D. Locus: Tca-3; RI Set: AKXL: 5: A; 6: A; 7: A; 8: A; 9: L; 12: L; 13: L; 14: A; 16: L; 17: A; 19: A; 21: L; 24: A; 25: L; 28: L; 29: L; 37: A; 38: A. Locus: Tca-3; RI Set: CXS; 1: C; 2: C; 3: S; 4: S; 5: S; 6: S; 7: S; 8: C; 9: S; 10: C; 11: S; 12: S; 13: C; 14: S. Locus: Tca-3; RI Set: OXA; 1: A; 2: A; 3: O; 4: A; 5: A; 6: A; 7: O; 8: O; 9: A; 10: O; 11: A; 12: A; 13: A; 14: A. Locus: Mip-1a; RI Set: BXD; 1: B; 2: D; 5: D; 6: B; 8: B; 9: D; 11: B; 12: D; 13: B; 14: D; 15: D; 16: D; 18: B; 19: D; 20: D; 21: D; 22: D; 23: B; 24: B; 25: B; 27: B; 28: B; 29: D; 30: B; 31: B; 32: O. Locus: Mip-1a; RI Set: AKXL; 5: A; 6: A; 7: A; 8: A; 9: L; 12: L; 13: L; 14: A; 16: A; 17: A; 19: A; 21: L; 24: A; 25: L; 28: L; 29: L; 37: A; 38: A. Locus: Mip-1b; RI Set: BXD; 1: B; 2: D; 5: D; 6: B; 8: B; 9: D; 11: B; 12: D; 13: B; 14: D; 15: D; 16: D; 18: B; 19: D; 20: D; 21: D; 22: D; 23: B; 24: B; 25: B; 27: B; 28: B; 29: O; 30: B; 31: B; 32: D. Locus: Mip-1b; RI Set: AKXL; 5: A; 6: A; 7: A; 8: A; 9: L; 12: L; 13: L; 14: A; 16: A; 17: A; 19: A; 21: L; 24: A; 25: L; 28: L; 29: L; 37: A; 38: A. Locus: Sigje; RI Set: CXS; 1: C; 2: C; 3: S; 4: C; 5: S; 6: S; 7: S; 8: C; 9: S; 10: C; 11: S; 12: S; 13: S; 14: S. Locus: Il-5; RI Set: BXD: 1: D; 2: D; 5: B; 6: D; 8: B; 9: B; 11: B; 12: D; 13: D; 14: D; 15: B; 16: D; 18: B; 19: B; 20: D; 21: D; 22: D; 23: B; 24: B; 25: B; 27: B; 28: D; 29: D; 30: B; 31: D; 32: O. Locus: Il-5; RI Set: CXS; 1: C; 2: C; 3: C; 4: C; 5: C; 6: S; 7: S; 8: C; 9: S; 10: S; 11: C; 12: C; 13: C; 14: S. Locus: Il-5; RI Set: OXA; 1: O; 2: O; 3: A; 4: A; 5: A; 6: A; 7: O; 8: O; 9: A; 10: O; 11: A; 12: A; 13: A; 14: O. |
