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Genomic organisation of the mouse Ret proto-oncogene
1Laboratorio di Genetica Molecolare, Istituto G. Gaslini, 16148 Genoa, Italy.
Abstract:
The RET proto-oncogene is involved in the development of both kidney and neural crests derived tissues. RET deleterious mutations cause hereditary neuroendocrine tumours and congenital intestinal aganglionosis. Ongoing efforts aimed at elucidating the function of this gene include expression studies in different species and in transgenic mice. As first step in the study of Ret expression in mouse, we obtained the mouse Ret genomic structure. Intron-exon boundaries were determined and sequenced, all introns but the first one were amplified and cloned, and exons positioned in a restriction map. Mouse and human genes comparison indicates a highly conserved genomic organisation, except for exon 21 which is not conserved in mouse. A region extending 386 bp 5' to the first exon was sequenced and compared with its human counterpart. Some features, reported for the human promoter, like the absence of TATA or CAAT boxes and a high GC content, are conserved.
Insights
Researchers detailed the mouse Ret gene structure, finding conserved genomic organization with humans, except for exon 21. This lays groundwork for studying the RET proto-oncogene
Area of Science:
- Genetics
- Molecular Biology
- Developmental Biology
Background:
- The RET proto-oncogene is crucial for kidney and neural crest development.
- RET gene mutations are linked to neuroendocrine tumors and congenital intestinal aganglionosis.
Purpose of the Study:
- To characterize the mouse Ret gene structure as a foundational step for expression studies.
- To compare the genomic organization of mouse and human RET genes.
Main Methods:
- Determined and sequenced intron-exon boundaries of the mouse Ret gene.
- Amplified, cloned, and mapped introns and exons.
- Sequenced and compared the 5' promoter region with the human counterpart.
Main Results:
- Established the complete intron-exon structure of the mouse Ret gene.
- Found high conservation in genomic organization between mouse and human RET genes.
- Identified exon 21 as a non-conserved region between species.
- Confirmed conserved features in the 5' promoter region, including high GC content and absence of TATA/CAAT boxes.
Conclusions:
- The mouse Ret gene structure has been elucidated.
- Genomic conservation provides a basis for comparative studies of RET function.
- The identified structural features offer insights into RET gene regulation.