Testis-specific Arf promoter expression in a transposase-aided BAC transgenic mouse model

Caroline Y. Sung, Yen Ting Liu, Lynda B. Bennett, Caitlin C. Devitt, Stephen X. Skapek

Research output: Contribution to journalArticle

Abstract

CDKN2A is an evolutionarily conserved gene encoding proteins implicated in tumor suppression, ocular development, aging, and metabolic diseases. Like the human form, mouse Cdkn2a encodes two distinct proteins—p16Ink4a, which blocks cyclin-dependent kinase activity, and p19Arf, which is best known as a positive regulator of the p53 tumor suppressor—and their functions have been well-studied in genetically engineered mouse models. Relatively little is known about how expression of the two transcripts is controlled in normal development and in certain disease states. To better understand their coordinate and transcript-specific expression in situ, we used a transposase-aided approach to generate a new BAC transgenic mouse model in which the first exons encoding Arf and Ink4a are replaced by fluorescent reporters. We show that mouse embryo fibroblasts generated from the transgenic lines faithfully display induction of each transgenic reporter in cell culture models, and we demonstrate the expected expression of the Arf reporter in the normal testis, one of the few places where that promoter is normally expressed. Interestingly, the TGFβ-2-dependent induction of the Arf reporter in the eye—a process essential for normal eye development—does not occur. Our findings illustrate the value of BAC transgenesis in mapping key regulatory elements in the mouse by revealing the genomic DNA required for Cdkn2a induction in cultured cells and the developing testis, and the apparent lack of elements driving expression in the developing eye.

Original languageEnglish (US)
Pages (from-to)6243-6252
Number of pages10
JournalMolecular Biology Reports
Volume46
Issue number6
DOIs
StatePublished - Dec 1 2019

Keywords

  • Arf
  • BAC transgenic mice
  • Cis-regulation
  • Eye development
  • Ink4a

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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