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.
Jishage
Kou-ichi
K
Pharmaceutical Technology Laboratory, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. jishagekui@chugai-pharm.co.jp
Nezu
Jun-ichi
J
Kawase
Yosuke
Y
Iwata
Takamitsu
T
Watanabe
Miho
M
Miyoshi
Akio
A
Ose
Asuka
A
Habu
Kiyoshi
K
Kake
Takei
T
Kamada
Nobuo
N
Ueda
Otoya
O
Kinoshita
Michiko
M
Jenne
Dieter E
DE
Shimane
Miyuki
M
Suzuki
Hiroshi
H
D055372:AMP-Activated Protein Kinases; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D017931:DNA Primers; D005314:Embryonic and Fetal Development / Q000235:genetics*; D007150:Immunohistochemistry; D007417:Intestinal Polyps / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010580:Peutz-Jeghers Syndrome / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases