| First Author | Hekmatnejad B | Year | 2014 |
| Journal | Gene | Volume | 538 |
| Issue | 2 | Pages | 328-33 |
| PubMed ID | 24440290 | Mgi Jnum | J:208796 |
| Mgi Id | MGI:5565043 | Doi | 10.1016/j.gene.2014.01.009 |
| Citation | Hekmatnejad B, et al. (2014) Altered gene dosage confirms the genetic interaction between FIAT and alphaNAC. Gene 538(2):328-33 |
| abstractText | Factor inhibiting ATF4-mediated transcription (FIAT) interacts with Nascent polypeptide associated complex and coregulator alpha (alphaNAC). In cultured osteoblastic cells, this interaction contributes to maximal FIAT-mediated inhibition of Osteocalcin (Ocn) gene transcription. We set out to demonstrate the physiological relevance of this interaction by altering gene dosage in compound Fiat and Naca (encoding alphaNAC) heterozygous mice. Compound Naca(+/-); Fiat(+/-) heterozygous animals were viable, developed normally, and exhibited no significant difference in body weight compared with control littermate genotypes. Animals with a single Fiat allele had reduced Fiat mRNA expression without changes in the expression of related family members. Expression of the osteocyte differentiation marker Dmp1 was elevated in compound heterozygotes. Static histomorphometry parameters were assessed at 8weeks of age using microcomputed tomography (muCT). Trabecular measurements were not different between genotypes. Cortical thickness and area were not affected by gene dosage, but we measured a significant increase in cortical porosity in compound heterozygous mice, without changes in biomechanical parameters. The bone phenotype of compound Naca(+/-); Fiat(+/-) heterozygotes confirms that FIAT and alphaNAC are part of a common genetic pathway and support a role for the FIAT/alphaNAC interaction in normal bone physiology. |
