Somatic forward genetic screens have the power to interrogate thousands of genes in a single animal. Retroviral and transposon mutagenesis systems in @entity19 have been designed and deployed in somatic tissues for surveying hematopoietic and solid @entity5 formation. In the context of @entity5 , the ability to visually mark mutant cells would present tremendous advantages for identifying @entity5 formation, monitoring @entity5 growth over time, and tracking @entity5 infiltrations and metastases into wild-type tissues. Furthermore, locating mutant clones is a prerequisite for screening and analyzing most other somatic phenotypes. For this purpose, we developed a system using the piggyBac (PB) transposon for somatic mutagenesis with an activated reporter and tracker, called PB-SMART. The PB-SMART @entity19 genetic screening system can simultaneously induce somatic mutations and mark mutated cells using bioluminescence or fluorescence. The marking of mutant cells enable analyses that are not possible with current somatic mutagenesis systems, such as tracking cell proliferation and @entity5 growth, detecting @entity5 cell infiltrations, and reporting tissue mutagenesis levels by a simple ex vivo visual readout. We demonstrate that PB-SMART is highly mutagenic, capable of @entity5 induction with low copy transposons, which facilitates the mapping and identification of causative insertions. We further integrated a conditional transposase with the PB-SMART system, permitting tissue-specific mutagenesis with a single cross to any available Cre line. Targeting the germline, the system could also be used to conduct F1 screens. With these features, PB-SMART provides an integrated platform for individual investigators to harness the power of somatic mutagenesis and phenotypic screens to decipher the genetic basis of @entity1 biology and disease.

piggyBac transposon somatic mutagenesis with an activated reporter and tracker (PB-SMART) for genetic screens in XXXX .

@entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity1 :: ('9606', 'Species') :: ['mammalian'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer']
@entity19 :: (10090,Species) :: ['mice']
