Gene Targeting of Desrt, a Novel ARID Class DNA-Binding Protein, Causes Growth Retardation and Abnormal Development of Reproductive Organs

  1. Mireille H. Lahoud1,
  2. Sika Ristevski1,
  3. Deon J. Venter3,4,
  4. Lars S. Jermiin5,8,
  5. Ivan Bertoncello3,
  6. Silva Zavarsek1,
  7. Sue Hasthorpe6,
  8. John Drago7,
  9. David de Kretser2,
  10. Paul J. Hertzog1,10,11, and
  11. Ismail Kola1,9
  1. 1Centre for Functional Genomics and Human Disease, and 2Molecular Reproduction and Endocrinology, Monash Institute of Reproduction and Development, Monash University, Melbourne, Victoria, Australia; 3Peter MacCallum Cancer Institute, East Melbourne, VIC 3002, Australia; 4Department of Pathology, University of Melbourne, Parkville, VIC 3052, Australia; 5John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia; 6F. Douglas Stephens Surgical Research Laboratory, Royal Children's Hospital, Parkville, VIC 3052, Australia; 7Department of Medicine, Monash University, Monash Medical Centre, Clayton, VIC 3168, Australia

Abstract

We have cloned and characterized a novel murine DNA-binding protein Desrt, with a motif characteristic of the ARID (A-Trich 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.

Footnotes

  • Present addresses: 8Australian Genomic Information Centre and School of Biological Sciences, The University of Sydney, Sydney, NSW 2006, Australia; 9Pharmacia Corporation, Kalamazoo, Michigan 49007, USA.

  • ↵10 Monash Institute of Reproduction and Development, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia.

  • ↵11 Corresponding author.

  • E-MAIL paul.hertzog{at}med.monash.edu.au; FAX 61-3-95947211.

  • Article published on-line before print: Genome Res., 10.1101/gr. 168801.

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.168801.

    • Received October 23, 2000.
    • Accepted May 2, 2001.
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  1. Published in Advance July 12, 2001, doi: 10.1101/gr.168801 Genome Res. 11: 1327-1334 Cold Spring Harbor Laboratory Press

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