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. Howev...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 13; pp. 8903 - 8908
Main Authors:	Jishage, Kou-ichi, Nezu, Jun-ichi, Kawase, Yosuke, Iwata, Takamitsu, Watanabe, Miho, Miyoshi, Akio, Ose, Asuka, Habu, Kiyoshi, Kake, Takei, Kamada, Nobuo, Ueda, Otoya, Kinoshita, Michiko, Jenne, Dieter E., Shimane, Miyuki, Suzuki, Hiroshi
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 25-06-2002 National Acad Sciences
Subjects:	Alleles AMP-Activated Protein Kinases Animals Antibodies Base Sequence Biological Sciences Blood cells Blotting, Northern Cloning, Molecular DNA Primers Embryonic and Fetal Development - genetics Embryos Exons Genes Genetic mutation Immunohistochemistry Intestinal Polyps - genetics Mice Mice, Knockout Molecular Sequence Data Peutz-Jeghers Syndrome - genetics Polymerase chain reaction Prenatal development Protein Serine-Threonine Kinases - genetics Reverse Transcriptase Polymerase Chain Reaction Stomach Tumors
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 To whom reprint requests should be addressed. E-mail: jishagekui@chugai-pharm.co.jp. Communicated by Takashi Sugimura, National Cancer Center, Tokyo, Japan Present address: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-13, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.122254599