Role of Lkb1, the causative gene of Peutz-Jegher's syndrome, in embryogenesis and polyposis.
Proc Natl Acad Sci U S A
; 99(13): 8903-8, 2002 Jun 25.
Article
in En
| MEDLINE
| ID: mdl-12060709
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peutz-Jeghers Syndrome
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Intestinal Polyps
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Protein Serine-Threonine Kinases
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Embryonic and Fetal Development
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2002
Document type:
Article
Affiliation country: