Pax: a murine multigene family of paired box-containing genes.

A murine multigene family has been identified that shares a conserved sequence motif, the paired box, with developmental control and tissue-specific genes of Drosophila. To date five murine paired box-containing genes (Pax genes) have been described and one, Pax-1, has been associated with the developmental mutant phenotype undulated. Here we describe the paired boxes of three novel Pax genes, Pax-4, Pax-5, and Pax-6. Comparison of the eight murine paired domains of the mouse, the five Drosophila paired domains, and the three human paired domains shows that they fall into six distinct classes: class I comprises Pox meso, Pax-1, and HuP48; class II paired, gooseberry-proximal, gooseberry-distal, Pax-3, Pax-7, HuP1, and HuP2; class III Pax-2, Pax-5, and Pax-8; class IV Pax-4; class V Pox neuro; and class VI Pax-6. Pax-1 and the human gene HuP48 have identical paired domains, as do Pax-3 and HuP2 as well as Pax-7 and HuP1, and are likely to represent homologous genes in mouse and man. Identical intron-exon structure and extensive sequence homology of their paired boxes suggest that several Pax genes represent paralogs. The chromosomal location of all novel Pax genes and of Pax-3 and Pax-7 has been determined and reveals that they are not clustered.

[1]  M. Noll,et al.  Conservation of the paired domain in metazoans and its structure in three isolated human genes. , 1989, The EMBO journal.

[2]  D. Duboule,et al.  A new homeo‐box is present in overlapping cosmid clones which define the mouse Hox‐1 locus. , 1986, The EMBO journal.

[3]  R. Auerbach.  Analysis of the developmental effects of a lethal mutation in the house mouse , 1954 .

[4]  Pierre Gönczy,et al.  A single amino acid can determine the DNA binding specificity of homeodomain proteins , 1989, Cell.

[5]  M. Goulding,et al.  The molecular basis of the undulated/Pax-1 mutation , 1991, Cell.

[6]  M. Scott,et al.  The structure and function of the homeodomain. , 1989, Biochimica et biophysica acta.

[7]  E. Knapik,et al.  Spatially and temporally restricted expression of Pax2 during murine neurogenesis. , 1990, Development.

[8]  P. Gruss,et al.  Murine developmental control genes. , 1990, Science.

[9]  F. Bonhomme,et al.  Investigation of genetic linkage between myosin and actin genes using an interspecific mouse back-cross , 1985, Nature.

[10]  J. Garnier,et al.  Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. , 1978, Journal of molecular biology.

[11]  H. Jäckle,et al.  The gooseberry–zipper region of Drosophila: five genes encode different spatially restricted transcripts in the embryo , 1987, The EMBO journal.

[12]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[13]  E. D. De Robertis,et al.  Vertebrate homeodomain proteins: families of region-specific transcription factors. , 1989, Trends in biochemical sciences.

[14]  D. Simon,et al.  Murine genes with homology to Drosophila segmentation genes. , 1988 .

[15]  P. D’Eustachio,et al.  Chromosomal localization of the Moloney sarcoma virus mouse cellular (c-mos) sequence , 1982, Journal of virology.

[16]  W. Noon,et al.  Intron splicing: a conserved internal signal in introns of animal pre-mRNAs. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Goulding,et al.  Pax‐3, a novel murine DNA binding protein expressed during early neurogenesis. , 1991, The EMBO journal.

[18]  N. Copeland,et al.  Genetic organization of the agouti region of the mouse. , 1987, Genetics.

[19]  J. Guénet,et al.  Chromosomal localization of the three members of the jun proto-oncogene family in mouse and man. , 1990, Oncogene.

[20]  H. Lehrach,et al.  Genetic and cytogenetic localisation of the homeo box containing genes on mouse chromosome 6 and human chromosome 7. , 1986, The EMBO journal.

[21]  J. Devereux,et al.  A comprehensive set of sequence analysis programs for the VAX , 1984, Nucleic Acids Res..

[22]  P. Gruss,et al.  The murine paired box gene, Pax7, is expressed specifically during the development of the nervous and muscular system , 1990, Mechanisms of Development.

[23]  D. Duboule,et al.  Hox-5.1 defines a homeobox-containing gene locus on mouse chromosome 2. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[24]  P. Ingham.  The molecular genetics of embryonic pattern formation in Drosophila , 1988, Nature.

[25]  M. Noll,et al.  Structure of the segmentation gene paired and the Drosophila PRD gene set as part of a gene network , 1986, Cell.

[26]  P. Gruss,et al.  Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system. , 1990, Development.

[27]  R. Balling,et al.  undulated, a mutation affecting the development of the mouse skeleton, has a point mutation in the paired box of Pax 1 , 1988, Cell.

[28]  Sean B. Carroll,et al.  The segmentation and homeotic gene network in early Drosophila development , 1987, Cell.

[29]  A. Joyner,et al.  En-1 and En-2, two mouse genes with sequence homology to the Drosophila engrailed gene: expression during embryogenesis. , 1987, Genes & development.

[30]  D. Threadgill,et al.  Regional localization of mouse Abl and Mos proto-oncogenes by in situ hybridization. , 1988, Genomics.

[31]  M. Scott,et al.  Structural relationships among genes that control development: sequence homology between the Antennapedia, Ultrabithorax, and fushi tarazu loci of Drosophila. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Guénet.  The contribution of wild derived mouse inbred strains to gene mapping methodology. , 1986, Current topics in microbiology and immunology.

[33]  P. Gruss,et al.  Pax 1, a member of a paired box homologous murine gene family, is expressed in segmented structures during development , 1988, Cell.

[34]  M. Noll,et al.  Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila , 1986, Cell.

[35]  C. Desplan,et al.  The paired box encodes a second DNA-binding domain in the paired homeo domain protein. , 1991, Genes & development.

[36]  N. Niikawa,et al.  Waardenburg syndrome type I in a child with de novo inversion (2)(q35q37.3). , 1989, American journal of medical genetics.

[37]  A. Read,et al.  Assignment of the locus for Waardenburg syndrome type I to human chromosome 2q37 and possible homology to the Splotch mouse. , 1990, American journal of human genetics.

[38]  D. Simon,et al.  Pax8, a murine paired box gene expressed in the developing excretory system and thyroid gland. , 1990, Development.

[39]  M. Akam,et al.  The molecular basis for metameric pattern in the Drosophila embryo. , 1987, Development.

[40]  M. Dickie.  NEW SPLOTCH ALLELES IN THE MOUSE. , 1964, The Journal of heredity.

[41]  P. Y. Chou,et al.  Empirical predictions of protein conformation. , 1978, Annual review of biochemistry.

[42]  S. Colowick,et al.  Methods in Enzymology , Vol , 1966 .

[43]  D. Duboule,et al.  The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes. , 1989, The EMBO journal.

[44]  M. Noll,et al.  Isolation of two tissue‐specific Drosophila paired box genes, Pox meso and Pox neuro. , 1989, The EMBO journal.

[45]  R B Jacobs.  Billion-dollar zeolite? , 1990, Science.

[46]  M. Justice,et al.  A molecular genetic linkage map of mouse chromosome 2. , 1990, Genomics.

[47]  A. Poustka,et al.  Lambda replacement vectors carrying polylinker sequences. , 1983, Journal of molecular biology.

[48]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[49]  C. Kappen,et al.  Mammalian homeobox-containing genes: genome organization, structure, expression and evolution. , 1988, The British journal of cancer. Supplement.

[50]  H. Lehrach,et al.  The HOX-5 and surfeit gene clusters are linked in the proximal portion of mouse chromosome 2. , 1990, Genomics.