| First Author | Pilz A | Year | 1993 |
| Journal | Mouse Genome | Volume | 91 |
| Issue | 4 | Pages | 882-84 |
| Mgi Jnum | J:16301 | Mgi Id | MGI:64385 |
| Citation | Pilz A, et al. (1993) Genetic mapping of the dipeptidylpeptidase IV gene on mouse Chromosome 2. Mouse Genome 91(4):882-84 |
| abstractText | Full text of Mouse Genome contribution: GENETIC MAPPING OF THE DIPEPTIDYLPEPTIDASE IV GENE ON MOUSE CHROMOSOME 2. Alison Pilz1, Dalila Darmoul2,3, Jo Peters4 and Cathy Abbott1,5. 1 Department of Genetics and Biometry, University College London, Wolfson House, 4, Stephenson Way, London, NW1 2HE, UK. 2 Unite de Biologie et Physiologie des Cellules Digestives, (Institut National de la Sante et de la Recherche Medicale U239), Faculte de Medicine Xavier Bichat, 16, Rue Henri Huchard, 75018 Paris, France. 3 MRC Human Biochemical Genetics Unit, Wolfson House, 4, Stephenson Way, London, NW1 2HE, UK. 4 MRC Radiobiology Unit, Chilton, Didcot, Oxon, OX11 ORD, UK. 5 MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK. Dipeptidylpeptidase IV (DPP4) belongs to a family of serine proteases which are responsible for the cleavage of dipeptides from the N-terminal ends of proteins. DPP4 is expressed in a variety of epithelial tissues, including intestine, kidney and liver (Hauri et al., 1985; Darmoul et al., 1992). The DPP4 gene has been localized to human chromosome 2 (HSA2), (Darmoul et al., 1990). The present report describes the use of an interspecific backcross to assign the Dpp-4 locus to mouse chromosome 2 (MMU2) and to determine the chromosomal location of the mouse homologue of the DPP4 gene in relation to other markers which map both to HSA2 and MMU2, namely Pax-8, Acra, Hoxd9 (previously known as Hox4.4), and Il-1b (Siracusa and Abbott, in press; see Table 1). In addition anonymous microsatellite markers were mapped to define further the location of the Dpp-4 gene. The interspecific backcross of 126 progeny used in this study between a laboratory inbred strain (C3H/AN) and Mus spretus has been described previously (Pilz et al., 1992). The gene markers used for Southern blot and PCR analysis of the cross are listed in Table 1. Southern blotting was carried out as in Pilz et al., 1992. PCR analysis of the cross was carried out as described in Abbott et al., (1992) for the Il-1b primers; as in Pilz et al., (1993) for the Hoxd9 primers, and as in Dietrich et al., (1992) for the D2Mit6, D2Mit8 and D2Mit11 primer pairs, except that PCR was carried out using Taq polymerase supplied by Advanced Biotechnologies in a volume of 50ul. Table 1. Loci names of markers used this study showing their location on HSA9, and RFLVs used for mapping MMU2. Name: dipeptidyl peptidase IV; Gene symbol: Mouse: Dpp-4, Human: DPP4; Human map Location: 2; Vector: pTZ18R; Insert size: 1.7kb SmaI; Fragment sizes (kb)a: C3H/AN: 9, 3.7, 3.5, 2; M. spretus: 9, 5, 2.7, 1.6. Name: acetylcholine receptor alpha; Gene symbol: Mouse: Acra, Human: CHRNA; Human map Location: 2q24-q32; Vector: pUC8; Insert size: 1.7kb EcoRI; Fragment sizes (kb)a: C3H/AN: 12, 8.5; M. spretus: 12, 6. Name: paired box gene-8; Gene symbol: Mouse: Pax-8, Human: PAX8; Human map Location: 2q12-q14; Vector: pBluescript; Insert size: 1.4kb EcoRV; Fragment sizes (kb)a: C3H/AN: 7, 4; M. spretus: 8, 7, 4. Name: homeobox D9; Gene symbol: Mouse: Hoxd9; Human: HOXD; Human map Location: 2q31-q32; *PCR marker. Name: interleukin-1 beta; Gene symbol: Mouse: Il-1b, Human: IL1B; Human map Location: 2q13-q21; *PCR marker. a Restriction fragments followed in the hackcross are underlined. *Hoxd9 and Il-1b were typed by PCR analysis. RFLVs between C3H/AN and Mus spretus were found with the restriction enzyme Pst1 for the Dpp-4, Acra and Pax-8 probes (see Table 1). The pedigree analysis of the 126 animals of the backcross is shown in Fig. 1. The number of mice carrying recombinant chromosomes for each pair of loci, based on minimizing the number of double recombinants, is:- D2Mit6 - 1 - Pax-8 - 18 - D2Mit8 - 4 - Dpp-4 - 6 - D2Mit11 - 5 - (Acra, Hoxd9) - 23 Ð Il-1b. Since 126 progeny were analysed the recombination distances (cM) +/- the standard error obtained between each pair of loci are:- D2Mit6 - 0.8 +/- 0.8 - Pax-8 - 14.3 +/- 3.1 - D2Mit8 - 3.2 +/- 1.6 - Dpp-4 - 4.8 +/- 1.9 - D2Mit11 - 4.0 +/- 1.7 - (Acra, Hoxd9) - 18.3 +/- 3.4 - Il-1b. Fig. 1 (Legend). Pedigree analysis of the 126 animals of the backcross (unfilled square) = C3H/AN; (filled square) = M. spretus. Each column is a diagrammatic representation of a particular chromosome. The linkage map produced by this study is shown in Fig. 2, along with selected markers from a consensus linkage map of MMU2 (Siracusa and Abbott, in press). Although single homologies between MMU2 and HSA9, HSA11, and HSA15 are shown, these markers represent considerable blocks of conserved synteny. The Pax-8, Dpp-4 and Il-lb genes map to three different regions of synteny with human chromosome 2q (see Fig. 2). There are three separate regions of synteny with human chromosome 2q; Pax-8 and Il-lb are located in the proximal and distal regions respectively, whereas Dpp-4 is positioned in the intermediate region which is the most extensive. The only other dipeptidylpeptidase which has been mapped in the mouse is Dpp-6 which has been assigned to MMU6 (Wada et al., 1993), suggesting that the Dpp loci are not clustered in the mouse genome. The chromosomal location of Dpp-4 on MMU2 is consistent with the location of the homologous human locus DPP4 on HSA2, (Darmoul et al., 1990) since this segment of MMU2 contains other genes with homologues on HSA2q (Fig. 2). The human GCG gene, which has been shown to map close to DPP4 on HSA2 (Darmoul et al., manuscript in preparation), has a mouse homologue (Gcg) which is likely to map near to Dpp-4 on MMU2 (Siracusa et al., 1990; Fig. 2). It would be interesting to map Gcg in the same cross as Dpp-4 to establish the gene order of these two markers on MMU2 relative to each other. This study of linkage mapping of the Dpp-4 gene extends our knowledge of linkage conservation between the mouse and human genomes. Acknowledgments. We are grateful to Dr. David Beeson for the gift of the Acra probe and to Prof. Peter Gruss for the gift of the Pax-8 probe. This work is supported by the MRC Human Genome Mapping Project, and the Association pour le Recherche Centre le Cancer. Fig. 2 (Legend). Linkage map obtained from this study. Certain markers from a consensus map (Siracusa and Abbott, 1993 in press) are also shown for comparison of gene order. Some markers with human homologues not located on HSA2 are shown in brackets (these selected markers represent regions of homology). Diagram not to scale. References. Abbott, C., Pilz, A., Moseley, H., and Peters, J. (1992). Mamm. Genome 3: 286-289. Darmoul, D., Lacasa, M., Cantret, I., Swallow, D.M., and Trugnan, G. (1990). Ann. Hum. Genet. 54: 191-197. Darmoul, D., Lacasa, M., Baricault, L., Marguet, D., Sapin, C., Trotot, P., Barbat, A., and Trugnan, G. (1992) J. Biol. Chem. 267: 4824-4833. Dietrich W., Katz, H., Lincoln, S.E., Shin, H-S., Friedman, J., Dracopoli, N., and Lander, E.S. (1992) Genetics 131: 423-447. Hauri, H.P., Sterchi, E.E., Bienz, F., Fransen, J., and Marxer, A. (1985) J. Cell Biol. 101: 838-851. Pilz, A., Moseley, H., Peters, J. and Abbott, C. (1992). Genomics 12: 715-719. Pilz, A.J. and Abbott, C.M. (1993) Mamm. Genome 4: 129-130. Siracusa, L. and Abbott, C. (1993). Mamm. Genome (in press). Siracusa, L.D., Silan, C.M., Justice, M.J., Mercer, J.A., Bauskin, A.R., Ben-Neriah, Y., Duboule, D., Hastie, N., Copeland, N.G., and Jenkins, N.A. (1990). Genomics 6: 491-504. Wada, K., Zimmerman, K.L., Adamson, M.C., Yokotani, N., Wenthold, R.J., and Kozak, C.A. (1993). Mamm. Genome 4: 234-237. |
