The tumor suppressor gene liver kinase B1 （LKB1）, also called STKll, encodes a serine/threonine kinase. LKB1 plays crucial roles in cell differentiation, proliferation, and polarity. In this study, LKB1 conditional knockout mice （LKB1pax2 CKO mice） were generated using Pax2-Cre mice to investigate the function of LKB1 in inner ear hair cells during early embryonic period. LKB1Pax2 CKO mice died perinatally. Immunofluorescence and scanning electron microscopy revealed that stereociliary bundles in LKB1Pax2 CKO mice were clustered and misoriented, respectively. Moreover, ectopic distribution of kinocilium bundles resulting from abnormal migration of kinocilium was observed in the mutant mice. The orientation of stereociliary bundles and the migration of kinocilia are critical indicators of planar cell polarity （PCP） of hair cells. LKB1 deficiency in LKB1Pax2 CKO mice thus disrupted hair cell planar polarity during embryonic development. Our results suggest that LKB1 is required in PCP formation in cochlear hair cells in mice.
Embryonic stem(ES)cells are widely used for different purposes,including gene targeting,cell therapy,tissue repair,organ regeneration,and so on.However,studies and applications of ES cells are hindered by ethical issues regarding cell sources.To circumvent ethical disputes,great efforts have been taken to generate ES cell-like cells,which are not derived from the inner cell mass of blastocyst-stage embryos.In 2006,Yamanaka et al.first reprogrammed mouse embryonic fibroblasts into ES cell-like cells called induced pluripotent stem(iPS)cells.About one year later,Yamanaka et al.and Thomson et al.independently reprogrammed human somatic cells into iPS cells.Since the first generation of iPS cells,they have now been derived from quite a few different kinds of cell types.In particular,the use of peripheral blood facilitates research on iPS cells because of safety,easy availability,and plenty of cell sources.Now iPS cells have been used for cell therapy,disease modeling,and drug discovery.In this review,we describe the generations,applications,potential issues,and future perspectives of iPS cells.
To solve the problem of embryonic lethality in conventional gene knockouts, site-specific recombinase （SSR） systems （Cre-loxP, FIp-FRT, and φC31） have been used for tissue-specific gene knockout. With the combination of an SSR system and inducible gene expression systems （tetracycline and tamoxifen）, stage-specific knockout and transgenic expression can be achieved. The application of this ＂SSR＋inducible＂ conditional tool to genomic manipulation can be extended in various ways. Alternatives to conditional gene targeting, such as conditional gene trapping, multipurpose conditional alleles, and conditional gene silencing, have been developed. SSR systems can also be used to construct precise disease models with point mutations and chromosomal abnormalities. With these exciting achievements, we are moving towards a new era in which the whole genome can be manipulated as we wish.
