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In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.

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What we have learnt about PIKE from the knockout mice.

Chi Bun Chan1, Keqiang Ye

  • 1Department of Pathology and Laboratory Medicine, Emory University School of Medicine Atlanta, GA USA.

International Journal of Biochemistry and Molecular Biology
|October 18, 2011
PubMed
Summary

Phosphoinositide 3-kinase enhancer (PIKE) proteins are GTPases with poorly understood roles. PIKE knockout mice reveal their involvement in multiple signaling pathways, impacting systemic homeostasis and organ development.

Keywords:
AdipocyteBDNFGluR2Insulin receptorLiverMammaryNeuronObesityPIKE

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • Phosphoinositide 3-kinase enhancer (PIKE) proteins, a GTPase family within the centaurin superfamily, have been known for over a decade.
  • Despite extensive research, the precise functions of PIKE proteins remain incompletely understood, particularly concerning their roles in organ development and systemic homeostasis.
  • Previous studies have elucidated some cellular functions, but in vivo physiological roles are only beginning to be explored.

Purpose of the Study:

  • To delineate the physiological roles of PIKE proteins using a PIKE knockout mouse model.
  • To investigate the involvement of PIKE in various signaling cascades beyond its known function as a PI3K/Akt enhancer.
  • To identify novel signaling pathways regulated by PIKE through in vivo observations.

Main Methods:

  • Generation and phenotypic characterization of PIKE knockout mice.
  • Analysis of signaling cascades including Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT), AMP-activated protein kinase (AMPK)/Acetyl-CoA carboxylase (ACC), and insulin receptor (IR)/Akt.
  • Review of current findings from PIKE knockout mouse studies.

Main Results:

  • PIKE knockout mice provide a valuable model for studying PIKE's physiological functions.
  • Phenotypic characterization revealed PIKE's involvement in multiple signaling pathways, including JAK/STAT, AMPK/ACC, and IR/Akt.
  • These in vivo findings suggest broader regulatory roles for PIKE in cellular signaling.

Conclusions:

  • PIKE proteins play critical roles in regulating multiple signaling cascades.
  • PIKE knockout mice are instrumental in uncovering novel physiological functions of PIKE.
  • Further research is warranted to fully elucidate the systemic and developmental impacts of PIKE signaling.