| 20869 |
Q9WTK7 |
STK11_MOUSE |
Serine/threonine-protein kinase STK11 (EC 2.7.11.1) (Liver kinase B1 homolog) (LKB1) (mLKB1) |
DISRUPTION PHENOTYPE |
Mice die in utero 8.5 to 9.5 dpc due to severe defects in their vasculature: embryos show neural tube defects, mesenchymal cell death, and vascular abnormalities. Extraembryonic development is also severely affected; the mutant placentas exhibit defective labyrinth layer development and the fetal vessels fail to invade the placenta. Male mice specifically lacking isoform 2 are sterile (PubMed:18774945). A specifically deletion in liver results in hyperglycemia with increased gluconeogenic and lipogenic gene expression due to loss of AMPK phosphorylation and subsequent dephosphorylation of CRTC2/TORC2 (PubMed:16308421). Use of a conditional allele, leads to defects in defects in axon formation with a thinner cortical wall and larger lateral ventricles in the brain cortex (PubMed:17482548). Heterozygous mice develop multiple gastric adenomatous polyps, with polyps remarkably similar to hamartomas of PJS patients both macroscopically and histologically. Polyps in the heterozygous mice are detected at 5 months, and cause premature lethality progressively from 8 months onwards. Polyps are most frequently observed in the stomach where they typically concentrate close to the pylorus. Polyps in the small and large intestine are significantly less frequent. The histology of the polyps in the heterozygous mice is remarkably similar to PJS polyps including the relative contribution of well-differentiated epithelium, and a prominent smooth muscle component. Ptgs2/Cox2 is highly up-regulated in heterozygous mice polyps concomitantly with activation of the extracellular signal-regulated kinases Mapk1/Erk2 and Mapk3/Erk1: treatment with celecoxib Ptgs2/Cox2 inhibitor significantly reduces the total polyp burden. {ECO:0000269|PubMed:11509733, ECO:0000269|PubMed:11956081, ECO:0000269|PubMed:12060709, ECO:0000269|PubMed:12218179, ECO:0000269|PubMed:12226664, ECO:0000269|PubMed:15480979, ECO:0000269|PubMed:16308421, ECO:0000269|PubMed:17482548, ECO:0000269|PubMed:18774945}. |