https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15121 Wed 11 Apr 2018 14:09:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18989 Sat 24 Mar 2018 08:05:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21602 cko) in somatic testicular cells to define the molecular mechanisms involved in the development of the testicular phenotype observed in PJS patients. Focal vacuolization in some of the seminiferous tubules was observed in 4-week-old mutant testes but germ cell development appeared to be normal. However, similar to PJS patients, we observed progressive germ cell loss and Sertoli cell only tubules in Lkb1^cko testes from mice older than 10 weeks, accompanied by defects in Sertoli cell polarity and testicular junctional complexes and decreased activation of the MAP/microtubule affinity regulating and focal adhesion kinases. Suppression of AMP kinase and activation of mammalian target of rapamycin (mTOR) signaling were also observed in Lkb1^cko testes. Loss of Tsc1 or Tsc2 copies the progressive Lkb1^cko phenotype, suggesting that dysregulated activation of mTOR contributes to the pathogenesis of the Lkb1^cko testicular phenotype. Pten^cko mice had a normal testicular phenotype, which could be explained by the comparative lack of mTOR activation detected. These studies describe the importance of LKB1 signaling in testicular biology and the possible molecular mechanisms driving the pathogenesis of the testicular defects observed in PJS patients.]]> Sat 24 Mar 2018 07:59:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20682 Sat 24 Mar 2018 07:55:42 AEDT ]]>