Gene targeting of Desrt, a novel ARID class DNA-binding protein, causes growth retardation and abnormal development of reproductive organs.

We have cloned and characterized a novel murine DNA-binding protein Desrt, with a motif characteristic of the ARID (A-T rich interaction domain) family of transcription factors. The Desrt gene encodes an 83-kD protein that is shown to bind DNA and is widely expressed in adult tissues. To examine the in vivo function of Desrt, we have generated mice with a targeted mutation in the ARID domain of Desrt. Homozygous mutants have reduced viability, pronounced growth retardation, and a high incidence of abnormalities of the female and male reproductive organs including cryptorchidism. This may thus serve as a model to dissect the mechanisms involved in the development of the reproductive tract including testicular descent. Gene-targeted mice also display a reduction in the thickness of the zona reticularis of the adrenal gland and transient aberrations of the T and B cell compartments of primary lymphoid organs. These data show that this novel DNA-binding protein, Desrt, has a nonredundant function during growth and in the development of the reproductive system.

[1]  R. Saint,et al.  The Drosophila dead ringer gene is required for early embryonic patterning through regulation of argos and buttonhead expression. , 1999, Development.

[2]  L. Parada,et al.  Cryptorchidism in mice mutant for Insl3 , 1999, Nature Genetics.

[3]  K. Itakura,et al.  The novel Mrf-2 DNA-binding domain recognizes a five-base core sequence through major and minor-groove contacts. , 1999, Biochemical and biophysical research communications.

[4]  I. Adham,et al.  Targeted disruption of the Insl3 gene causes bilateral cryptorchidism. , 1999, Molecular endocrinology.

[5]  L. Moore,et al.  The trithorax group gene osa encodes an ARID-domain protein that genetically interacts with the brahma chromatin-remodeling factor to regulate transcription. , 1999, Development.

[6]  A. Courey,et al.  Dorsal-Mediated Repression Requires the Formation of a Multiprotein Repression Complex at the Ventral Silencer , 1998, Molecular and Cellular Biology.

[7]  Yate-Ching Yuan,et al.  A novel DNA-binding motif shares structural homology to DNA replication and repair nucleases and polymerases , 1998, Nature Structural Biology.

[8]  P. Dallas,et al.  p300/CREB Binding Protein-Related Protein p270 Is a Component of Mammalian SWI/SNF Complexes , 1998, Molecular and Cellular Biology.

[9]  A. Rustighi,et al.  NF-kappaB mediated transcriptional activation is enhanced by the architectural factor HMGI-C. , 1998, Nucleic acids research.

[10]  I. Kola,et al.  Cloning and Characterization of Soluble and Transmembrane Isoforms of a Novel Component of the Murine Type I Interferon Receptor, IFNAR 2* , 1997, The Journal of Biological Chemistry.

[11]  G M Rubin,et al.  eyelid antagonizes wingless signaling during Drosophila development and has homology to the Bright family of DNA-binding proteins. , 1997, Genes & development.

[12]  N. Ling,et al.  Immunosuppressive phenotype of corticotropin-releasing factor transgenic mice is reversed by adrenalectomy. , 1997, Cellular immunology.

[13]  R. Saint,et al.  Characterization of the dead ringer gene identifies a novel, highly conserved family of sequence-specific DNA-binding proteins , 1996, Molecular and cellular biology.

[14]  M. Tymms,et al.  Construction of a mouse blastocyst cDNA library by PCR amplification from total RNA , 1996, Molecular reproduction and development.

[15]  Dimitris Thanos,et al.  Reversal of intrinsic DNA bends in the IFNβ gene enhancer by transcription factors and the architectural protein HMG I(Y) , 1995, Cell.

[16]  R. Scheuermann,et al.  The immunoglobulin heavy-chain matrix-associating regions are bound by Bright: a B cell-specific trans-activator that describes a new DNA-binding protein family. , 1995, Genes & development.

[17]  Xianjin Zhou,et al.  Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C , 1995, Nature.

[18]  T. Takeuchi,et al.  Gene trap capture of a novel mouse gene, jumonji, required for neural tube formation. , 1995, Genes & development.

[19]  Ross A. Overbeek,et al.  The genetic data environment an expandable GUI for multiple sequence analysis , 1994, Comput. Appl. Biosci..

[20]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[21]  K. Chada,et al.  Mini-mouse: phenotypic characterization of a transgenic insertional mutant allelic to pygmy. , 1994, Genetical research.

[22]  H. Chiba,et al.  Two human homologues of Saccharomyces cerevisiae SWI2/SNF2 and Drosophila brahma are transcriptional coactivators cooperating with the estrogen receptor and the retinoic acid receptor. , 1994, Nucleic acids research.

[23]  M. Scott,et al.  Five SWI/SNF gene products are components of a large multisubunit complex required for transcriptional enhancement. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[24]  L. Powell-Braxton,et al.  IGF-I is required for normal embryonic growth in mice. , 1993, Genes & development.

[25]  J. Baker,et al.  Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r) , 1993, Cell.

[26]  Elizabeth J. Robertson,et al.  Role of insulin-like growth factors in embryonic and postnatal growth , 1993, Cell.

[27]  Rudolf Jaenisch,et al.  Targeted mutation of the DNA methyltransferase gene results in embryonic lethality , 1992, Cell.

[28]  T. Roszman,et al.  Immunologic disparity in the hypopituitary dwarf mouse. , 1992, Journal of immunology.

[29]  M. Nissen,et al.  The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. , 1990, The Journal of biological chemistry.