Multiple endocrine neoplasia-like syndrome (MENX) is a hereditary cancer syndrome in the rat characterized by multiple tumors affecting the neuroendocrine system developed within the first year of life. The spectrum of affected organs overlaps MEN1 and MEN2 syndromes in human, but, in contrast to them, MENX is inherited as a recessive trait. Unlike MEN variants known in man, MENX is also characterized by an inborn bilateral cataract. This work presents the mapping of the MENX locus to rat chromosome 4 by a genome-wide linkage analysis and a selection of candidate genes based on the data available in electronic genetic resources. The mapping of the MENX locus was done in 41 animals obtained from a (Wistar/Nhg x SDwe) x SDwe interstrain backcross, where SDwe (Sprague-Dawley white eye) indicates the affected animals. Initial screening of the rat genome using microsatellite markers revealed linkage with the disease phenotype with chromosome 4. No linkage was found on rat chromosome 1 where rat homologue of MEN1 is located - gene known to be responsible for multiple endocrine neoplasia type 1 in man. The MENX disease locus was initially mapped to an approximately 22cM large interval including RET gene known to be involved in the development of human MEN2A and MEN2B syndromes. In order to find out about the potential involvement of RET in MENX, several microsatellite markers located in the proximity of RET were analyzed for linkage to the disease phenotype. The result of this analysis excluded RET from the critical region on rat chromosome 4. Additional informative microsatellites were used to restrict the region of interest leading ultimately to the mapping of the MENX gene to an approximately 9cM interval. The data presented in this work shows that the gene involved in MENX and possibly in other endocrine tumors is located within the distal part of rat chromosome 4. Analysis of the human syntenic regions did not identify genes involved in the structure or function of the neuroendocrine organs, neither did it identify genes playing role in the development or pathology of the eye. Generation of additional recombinant animals, studies on the expression of the candidate genes in the affected tissues, as well as the use of online genetic tools and resources which are continuously being improved should enable the identification of the MENX gene and further on contribute to our understanding of the genetic mechanisms of neuroendocrine tissue tumorigenesis.     «

Multiple endocrine neoplasia-like syndrome (MENX) is a hereditary cancer syndrome in the rat characterized by multiple tumors affecting the neuroendocrine system developed within the first year of life. The spectrum of affected organs overlaps MEN1 and MEN2 syndromes in human, but, in contrast to them, MENX is inherited as a recessive trait. Unlike MEN variants known in man, MENX is also characterized by an inborn bilateral cataract. This work presents the mapping of the MENX locus to rat chromo...     »

Das der Multiplen Endokrinen Neoplasie ähnliche Syndrom (MENX) ist ein erbliches Krebssyndrom der Ratte, welches durch mehrere neuroendokrine Tumore charakterisiert ist. Im Gegensatz zu MEN1 und MEN2 Syndrome beim Menschen wird MENX rezessiv vererbt, außerdem tritt bei MENX noch ein angeborener, beidseitigen Katarakt auf. Diese Arbeit zeigt sowohl die Kartierung des MENX Lokus auf dem circa 9cM großem Intervall des Rattenchromosoms 4 durch eine Genom-weite Kopplungsanalyse, als auch die Selektion der in Frage kommenden Gene mit Hilfe der Daten, die in den öffentlich zugänglichen Gendatenbanken vorhanden sind.     «

Das der Multiplen Endokrinen Neoplasie ähnliche Syndrom (MENX) ist ein erbliches Krebssyndrom der Ratte, welches durch mehrere neuroendokrine Tumore charakterisiert ist. Im Gegensatz zu MEN1 und MEN2 Syndrome beim Menschen wird MENX rezessiv vererbt, außerdem tritt bei MENX noch ein angeborener, beidseitigen Katarakt auf. Diese Arbeit zeigt sowohl die Kartierung des MENX Lokus auf dem circa 9cM großem Intervall des Rattenchromosoms 4 durch eine Genom-weite Kopplungsanalyse, als auch die Selektio...     »