Abstract
The analysis of yeast artificial chromosomes (YACs) containing the complete mouse casein gene locus revealed the presence of five casein genes, α -, ß-, γ -, δ-, and κ-casein, in this order, in the locus. The a- and ß-casein genes are only 10 kb apart and have convergent transcriptional orientations. The distance between the ß-casein gene and the αs2-like γ-casein gene is about 70 kb, and these genes have divergent transcriptional orientations. The γ - and δ-casein genes, both encoding a αs2-like casein, are linked within 60 kb and convergently transcribed. The κ-casein gene is located about 100 kb from the δ-gene. Except for the presence of the δ-casein gene, the organization of the mouse casein locus resembles that of the bovine locus, including the transcriptional orientation of the genes. In contrast to the other casein genes, which are strongly induced at mid-lactation, expression of the 8-casein gene is abruptly induced upon parturition. Comparative analysis of αs2-like sequences from various species suggests that the ancestral αs2-like gene duplicated around the time of radiation of the rodent and artiodactylid ancestors.
Similar content being viewed by others
References
Alexander, L.J., Das, G.N., Beattie, C.W. (1992). The sequence of porcine alpha s2-casein cDNA. Anim. Genet. 23, 365–367.
Altschul, S.F., Gish, W., Miller, W., Myers, E.W., Lipman, D.J. (1990). Basic local alignment search tool. J. Mol. Biol. 215, 403–410.
Anand, R., Villasante, A., Tyler-Smith, C. (1989). Construction of yeast artificial chromosome libraries with large inserts using fractionation by pulsed field gel electrophoresis. Nucleic Acids Res. 17, 3425–3433.
Boisnard, M., Hue, D., Bouniol, C., Mercier, J.C., Gaye, P. (1991). Multiple mRNA species code for two non-allelic forms of ovine alpha s2-casein. Eur. J. Biochem. 201, 633–641.
Bonsing, J., Mackinlay, A.G. (1987). Recent studies on nucleotide sequences encoding the caseins. J. Dairy Res. 54, 447–461.
Boudreau, N., Myers, C., Bissell, M.J. (1995). From laminin to lamin: regulation of tissue-specific gene expression by the EC.M. Trends Cell Biol. 5, 1–4.
Bouniol, C. (1993). Sequence of the goat alpha s2-casein-encoding cDNA. Gene 125, 235–236.
Bouniol, C., Printz, C., Mercier, J.C. (1993). Bovine alpha s2-casein D is generated by exon VIII skipping. Gene 128, 289–293.
Chu, G., Vollrath, D., Davis R.W. (1986). Separation of large DNA molecules by contour-clamped homologous electric fields. Science 234, 1582–1585.
Church, G.M., Gilbert, W. (1984). Genomic sequencing. Proc. Natl. Acad. Sci. USA 81, 1991–1995.
Dawson, S.P., Wilde, C.J., Tighe, P.J., Mayer, R.J. (1993). Characterization of two novel casein transcripts in rabbit mammary gland. Biochem. J. 296, 777–784.
den Dunnen, J.T., van Ommen, G.-J.B. (1991). Pulsed-field gel electrophoresis. In Protocols in Human Molecular Genetics, C. Mathew, ed. Vol. 9 (Clifton, UK: The Humana Press Inc.), pp. 169–182.
Doppler, W., Hock, W., Hofer, P., Groner, B., Ball, R.K. (1990). Prolactin and glucocorticoid hormones control transcription of the beta-casein gene by kinetically distinct mechanisms. Mol. Endocrinol. 4, 912–919.
Felsenstein, J. (1981). Evolutionary trees from DNA sequences: a maximum likelihood approach. J. Mol. Evol. 17, 368–376.
Gallagher, D.S., Schelling, C.P., Groenen, M.M., Womack, J.E. (1994). Confirmation that the casein gene cluster resides on cattle chromosome 6. Mamm. Genome 5, 524.
Groenen, M.A., Dijkhof, R.J., van der Poel, J.J., van Diggelen, R., Verstege, E. (1992). Multiple octamer binding sites in the promoter region of the bovine alpha s2-casein gene. Nucleic Acids Res. 20, 4311–4318.
Groenen, M.A., Dijkhof, R.J., Verstege, A.J., van der Poel, J.J. (1993). The complete sequence of the gene encoding bovine alpha s2-casein. Gene 123, 187–193.
Groner, B., Gouilleux, F. (1995). Prolactin-mediated gene activation in mammary epithelial cells. Curr. Opin. Genet. Dev. 5, 587–594.
Groner, B., Altiok, S., Meier, V. (1994). Hormonal regulation of transcription factor activity in mammary epithelial cells. Mol. Cell. Endocrinol. 100, 109–114.
Gupta, P., Rosen, J.M., D’Eustachio, P., Ruddle, F.H. (1982). Localization of the casein gene family to a single mouse chromosome. J. Cell Biol. 93, 199–204.
Hall, L., Laird, J.R., Pascall, J.C., Craig, R.K. (1984). Guinea-pig casein cDNA. Nucleotide sequence analysis and comparison of the deduced protein sequence with that of bovine alpha s2 casein. Eur. J. Biochem. 1138, 585–589.
Hennighausen, L.G., Sippel, A.E. (1982). Characterization and cloning of the mRNAs specific for the lactating mouse mammary gland. Eur. J. Biochem. 125, 131–141.
Hennighausen, L.G., Steudle, A., Sippel, A.E. (1982). Nucleotide sequence of cloned cDNA coding for mouse epsilon casein. Eur. J. Biochem. 126, 569–572.
Higgins, D.G. (1994). CLUSTAL V: multiple alignment of DNA and protein sequences. Methods Mol. Biol. 25, 307–318.
Hobbs, A.A., Rosen, J.M. (1982). Sequence of rat alpha- and gamma-casein mRNAs: evolutionary comparison of the calcium-dependent rat casein multigene family. Nucleic Acids Res. 10, 8079–8098.
Larin, Z., Monaco, A.P., Lerhach, H. (1991). Yeast artificial chromosome libraries containing large inserts from mouse and human DNA. Proc. Natl. Acad. Sci. USA 88, 4123–4127.
Leroux, C., Mazure, N., Martin, P. (1992). Mutations away from splice site recognition sequences might cis-modulate alternative splicing of goat alpha sl-casein transcripts. Structural organization of the relevant gene. J. Biol. Chem. 267, 6147–6157.
Menon, R.S., Chang, Y.F., Jeffers, K.F., Ham, R.G. (1992). Exon skipping in human beta-casein. Genomics 12, 13–17.
Mercier, J.-C., Vilotte, J.-L. (1993). Structure and function of milk protein genes. J. Dairy Sci. 76, 3079–3098.
Raught, B., Liao, S.-L., Rosen, J.M. (1995). Developmentally and hormonally regulated CCAAT/enhancer-binding protein isoforms influence beta-casein gene expression. Mol. Endocrinol. 9, 1223–1232.
Rijnkels, M., Kooiman, P.M., Krimpenfort, P.J.A., de Boer, H.A., Pieper, F.R. (1995). Expression analysis of the individual bovine beta-, alpha s2- and kappa-casein genes in transgenic mice. Biochem. J. 311, 929–937.
Rijnkels, M., Kooiman, P.M., de Boer, H.A., Pieper, F.R. Organization of the bovine casein gene locus. Mamm. Genome (in press).
Sasaki, T., Sasaki, M., Enami, J. (1993). Mouse gamma-casein cDNA: PCR cloning and sequence analysis. Zool. Sci. 10, 65–72.
Schmidhauser, C., Casperson, G.F., Myers, C.A., Sanzo, K.T., Bolten, S., Bissell, M.J. (1992). A novel transcriptional enhancer is involved in the prolactin- and extracellular matrix-dependent regulation of beta-casein gene expression. Mol. Biol. Cell 3, 699–709.
Smith, S.W., Overbeek, R., Woese, C.R., Gilbert, W., Gillevet, P.M. (1994). The genetic data environment an expandable GUI for multiple sequence analysis. Comput. Appl. Biosci. 10, 671–675.
Snyder, M., Hunkapiller, M., Yuen, D., Silvert, D., Fristrom, J., Davidson, N. (1982). Cuticle protein genes of Drosophila: structure, organization and evolution of four clustered genes. Cell 29, 1027–1040.
Stewart, A.F., Bonsing, J., Beattie, C.W., Shah, F., Willis, I.M., MacKinlay, A.G. (1987) Complete nucleotide sequences of bovine alpha S2- and beta-casein cDNAs: comparisons with related sequences in other species. Mol. Biol. Evol. 4, 231–241.
Thompson, M.D., Dave, J.R., Nakhasi, H.L. (1985). Molecular cloning of mouse mammary gland kappa-casein: comparison with rat kappa-casein and rat and human gamma-fibrinogen. DNA 4, 263–271.
Yoshimura, M. and Oka, T. (1989). Isolation and structural analysis of the mouse beta-casein gene. Gene 78, 267–275.
Zucht, H.D., Raida, K., Adaermann, K., Magert, H J., Frossmann, W.G. (1995). Casocidin-I: a casein-alpha s2 derived peptide exhibits antibacterial activity. FEBS Lett. 372, 185–188.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rijnkels, M., Wheeler, D.A., de Boer, H.A. et al. Structure and expression of the mouse casein gene locus. Mammalian Genome 8, 9–15 (1997). https://doi.org/10.1007/s003359900338
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s003359900338