Changes in hepatic gene expression in dogs with experimentally induced nutritional iron deficiency.
OBJECTIVE
We investigated hepatic gene expression in dogs with experimentally induced nutritional iron deficiency (ID). Our hypothesis was that ID would result in decreased hepcidin gene expression, and possibly in altered expression of other genes associated with iron metabolism.


METHODS
Liver biopsies were collected from each of 3 dogs before induction of ID, at the point of maximal ID, and after resolution of ID. Using Affymetrix microarray technology and analytical tools specifically designed for microarray data, we identified genes that had at least a 2-fold change in expression in response to ID. Four genes were selected for further analysis by reverse transcriptase PCR (RT-PCR).


RESULTS
Dogs with ID had markedly decreased expression of the hepcidin gene (mean decrease of 40-fold for one probe and >100-fold for another probe) and increased expression of the transferrin receptor gene (mean increase of >7-fold). There was also mildly decreased expression of the "similar to calreticulin" gene and a gene of unknown function. Results of RT-PCR analysis were consistent with microarray findings.


CONCLUSIONS
Changes in hepcidin and transferrin receptor gene expression were consistent with the known biology of iron metabolism. The decrease in expression of a gene identified as "similar to calreticulin," while not statistically significant, was consistent with the findings of other investigators that suggest iron plays a role in calreticulin expression.
Fry
Michael M
MM
Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996-4542, USA. mfry@utk.edu
Kirk
Claudia A
CA
Liggett
Jason L
JL
Daniel
Gregory B
GB
Baek
Seung Joon
SJ
Gouffon
Julia S
JS
Chimakurthy
Pradeep M
PM
Rekapalli
Bhanu
B
D018798:Anemia, Iron-Deficiency / Q000378:metabolism / Q000662:veterinary*; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D019266:Iron, Dietary; D008099:Liver / Q000378:metabolism*; D008297:Male
D019266:Iron, Dietary