Role of Lkb1 , the causative gene of Peutz–Jegher's syndrome, in embryogenesis and polyposis
Copyright policy )Role of Lkb1 , the causative gene of Peutz–Jegher's syndrome, in embryogenesis and polyposis
Peutz–Jeghers syndrome (PJS) is a dominantly inherited human disorder characterized by gastrointestinal hamartomatous polyposis and mucocutaneous melanin pigmentation. LKB1 (STK11) serine/threonine kinase is the product of the causative gene of PJS, which has been mapped to chromosome 19p13.3. However, several studies have produced results that are not consistent with a link between LKB1 gene mutation and PJS. We constructed a knockout gene mutation of Lkb1 to determine whether it is the causative gene of PJS and to examine the biological role of the Lkb1 gene. Lkb1 −/− mice died in utero between 8.5 and 9.5 days postcoitum. At 9.0 days postcoitum, Lkb1 −/− embryos were generally smaller than their age-matched littermates, showed developmental retardation, and did not undergo embryonic turning. Multiple gastric adenomatous polyps were observed in 10- to 14-month-old Lkb1 +/− mice. Our results indicate that functional Lkb1 is required for normal embryogenesis and that it is related to tumor development. The Lkb1 +/− mouse is suitable for studying molecular mechanism underlying the development of inherited gastric tumors in PJS.
- Max Planck Institute of Psychiatry Germany
- Chugai Pharmaceutical Co. Japan
- Max Planck Society Germany
Mice, Knockout, Base Sequence, Reverse Transcriptase Polymerase Chain Reaction, Molecular Sequence Data, Peutz-Jeghers Syndrome, Intestinal Polyps, AMP-Activated Protein Kinases, Protein Serine-Threonine Kinases, Blotting, Northern, Immunohistochemistry, Embryonic and Fetal Development, Mice, Animals, Cloning, Molecular, DNA Primers
Mice, Knockout, Base Sequence, Reverse Transcriptase Polymerase Chain Reaction, Molecular Sequence Data, Peutz-Jeghers Syndrome, Intestinal Polyps, AMP-Activated Protein Kinases, Protein Serine-Threonine Kinases, Blotting, Northern, Immunohistochemistry, Embryonic and Fetal Development, Mice, Animals, Cloning, Molecular, DNA Primers
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