Generation of animals allowing the conditional inactivation of the Pax4 gene

Simon Kordowich1, Palle Serup, Patrick Collombat

  • 1Department of Molecular Cell Biology, Max-Planck Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen, Germany.

Transgenic Research
|June 22, 2012
PubMed

Insights

Paired-box 4 (Pax4) is vital for creating insulin-producing beta-cells in the pancreas. Conditional knockout mice will now allow studying Pax4

Area of Science:

  • Endocrinology
  • Developmental Biology
  • Genetics

Background:

  • Paired-box 4 (Pax4) is a transcription factor crucial for endocrine pancreas development.
  • Pax4 is essential for the generation of insulin-producing beta-cells.
  • The role of Pax4 in adult endocrine cells and the central nervous system is largely unknown.

Purpose of the Study:

  • To investigate the function of Pax4 in mature beta-cells.
  • To explore the role of Pax4 in the adult central nervous system.
  • To generate a tool for conditional knockout of Pax4 in adult tissues.

Main Methods:

  • Generation of Pax4 conditional knockout mice.
  • Analysis of Pax4 function using loss-of-function models.
  • Study of Pax4 misexpression in glucagon-expressing cells.

Main Results:

  • Pax4 is indispensable for beta-cell development.
  • Misexpression of Pax4 can regenerate beta-cells and reverse chemically induced diabetes.
  • Conditional knockout mice enable targeted analysis of Pax4 in adult tissues.

Conclusions:

  • Pax4 plays a critical role in beta-cell biology.
  • Pax4 has potential therapeutic applications for diabetes.
  • Conditional knockout models are essential for studying gene function in adult systems.