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Mapping of a novel MEN-like syndrome locus to rat Chromosome 4

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Abstract

Multiple endocrine neoplasia-like syndrome (MENX) is a hereditary cancer syndrome in the rat characterized by inborn cataract and multiple tumors affecting the neuroendocrine system developed within the first year of life. The spectrum of affected organs is intermediate between MEN type 1 (MEN1) and MEN type 2 (MEN2) syndromes in human, but, in contrast to them, MENX is inherited in a recessive fashion. Here we report the mapping of the MENX locus to rat Chromosome (Chr) 4 by a genome-wide linkage analysis. This analysis was done in 41 animals obtained from a (Wistar/Nhg × SDwe) × SDwe interstrain backcross, where SDwe (Sprague-Dawley white eye) indicates the affected animals. The MENX disease locus was ultimately mapped to a ~22-cM interval on Chr 4 that includes the rat homolog of the human RET proto-oncogene. As activating point mutations of RET are known to be responsible for MEN2 in human, we analyzed several markers located in the proximity of Ret for linkage to the disease phenotype. Our data exclude Ret involvement in MENX and establish that a second gene, playing a role in endocrine tumor formation, lies within the distal part of rat Chr 4. Although heritable human endocrine tumors are quite rare, sporadic tumors of MEN-affected tissues occur at a much higher frequency, and their pathogenesis is poorly understood. The identification of the MENX gene should contribute to our understanding of the genetic mechanisms of neuroendocrine tissue tumorigenesis and may assist in developing new and more appropriate therapeutic strategies for these diseases.

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Acknowledgements

We thank Elenore Samson, Jacqueline Müller, and Kornelia Fieder for their expert technical assistance and animal husbandry skills. The project is funded by DFG Graduierten Kolleg 333.

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Authors and Affiliations

  1. Institute of Pathology, GSF-National Research Center for Environment and Health, D-85764 Neuherberg, Germany

    Kamilla Piotrowska, Natalia S. Pellegata, Michael Rosemann, Andreas Fritz & Michael J. Atkinson

  2. Institute of Developmental Genetics, GSF-National Research Center for Environment and Health, D-85764 Neuherberg, Germany

    Jochen Graw

Authors
  1. Kamilla Piotrowska
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  2. Natalia S. Pellegata
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  3. Michael Rosemann
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  4. Andreas Fritz
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  5. Jochen Graw
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  6. Michael J. Atkinson
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Corresponding author

Correspondence to Michael J. Atkinson.

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Piotrowska, K., S. Pellegata, N., Rosemann, M. et al. Mapping of a novel MEN-like syndrome locus to rat Chromosome 4 . Mamm Genome 15, 135–141 (2004). https://doi.org/10.1007/s00335-003-3027-8

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  • DOI: https://doi.org/10.1007/s00335-003-3027-8

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