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An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
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Altered gene dosage confirms the genetic interaction between FIAT and αNAC

Bahareh Hekmatnejad1, Vice Mandic1, Vionnie W C Yu1

  • 1Research Unit, Shriners Hospital for Children - Canada, Montreal, Quebec H3G 1A6, Canada; Department of Human Genetics, McGill University, Montreal, Quebec H3A 2T5, Canada.

Gene
|January 21, 2014
PubMed

Insights

The interaction between Factor Inhibiting ATF4-mediated Transcription (FIAT) and αNAC impacts bone physiology. Compound heterozygous mice showed increased cortical porosity, confirming FIAT and αNAC

Area of Science:

  • Bone Biology
  • Molecular Genetics
  • Gene Regulation

Background:

  • Factor inhibiting ATF4-mediated transcription (FIAT) interacts with Nascent polypeptide associated complex and coregulator alpha (αNAC).
  • This interaction is known to inhibit Osteocalcin (Ocn) gene transcription in osteoblastic cells.

Purpose of the Study:

  • To investigate the physiological role of the FIAT/αNAC interaction in vivo.
  • To determine the impact of reduced FIAT and αNAC gene dosage on bone structure and function.

Main Methods:

  • Generation and analysis of compound Naca(+/-); Fiat(+/-) heterozygous mice.
  • Assessment of gene expression, bone histomorphometry using microcomputed tomography (μCT), and biomechanical testing.

Main Results:

  • Compound heterozygotes exhibited elevated expression of the osteocyte marker Dmp1.
  • A significant increase in cortical porosity was observed in compound heterozygous mice.
  • No significant changes in trabecular bone parameters, cortical thickness, or biomechanical properties were found.

Conclusions:

  • The FIAT/αNAC interaction is part of a common genetic pathway influencing bone physiology.
  • This study supports a role for the FIAT/αNAC complex in regulating normal bone structure, specifically cortical bone characteristics.
Keywords:
BoneCortical porosityFactor inhibiting ATF4-mediated transcription (FIAT)Nascent polypeptide associated complex and coregulator alpha (αNAC)

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