Abstract
Hereditary hemochromatosis is an iron overload disorder most commonly caused by a defect in the HFE gene. While the genetic defect is highly prevalent, the majority of individuals do not develop clinically significant iron overload, suggesting the importance of genetic modifiers. Murine hfe knockout models have demonstrated that strain background has a strong effect on the severity of iron loading. We noted that hepatic iron loading in hfe−/− mice occurs primarily over the first postnatal weeks (loading phase) followed by a timeframe of relatively static iron concentrations (plateau phase). We thus evaluated the effects of background strain and of age on hepatic gene expression in Hfe knockout mice (hfe−/−). Hepatic gene expression profiles were examined using cDNA microarrays in 4- and 8-week-old hfe−/− and wild-type mice on two different genetic backgrounds, C57BL/6J (C57) and AKR/J (AKR). Genes differentially regulated in all hfe−/− mice groups, compared with wild-type mice, including those involved in cell survival, stress and damage responses and lipid metabolism. AKR strain-specific changes in lipid metabolism genes and C57 strain-specific changes in cell adhesion and extracellular matrix protein genes were detected in hfe−/− mice. Mouse strain and age are each significantly associated with hepatic gene expression profiles in hfe−/− mice. These affects may underlie or reflect differences in iron loading in these mice.
| Original language | English |
|---|---|
| Pages (from-to) | 1-9 |
| Number of pages | 9 |
| Journal | Genes and Nutrition |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2015 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Genetics
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Effects of strain and age on hepatic gene expression profiles in murine models of HFE-associated hereditary hemochromatosis. / Lee, Seung Min; Loguinov, Alexandre; Fleming, Robert E.; Vulpe, Christopher D.
In: Genes and Nutrition, Vol. 10, No. 1, 01.01.2015, p. 1-9.Research output: Contribution to journal › Article
TY - JOUR
T1 - Effects of strain and age on hepatic gene expression profiles in murine models of HFE-associated hereditary hemochromatosis
AU - Lee, Seung Min
AU - Loguinov, Alexandre
AU - Fleming, Robert E.
AU - Vulpe, Christopher D.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Hereditary hemochromatosis is an iron overload disorder most commonly caused by a defect in the HFE gene. While the genetic defect is highly prevalent, the majority of individuals do not develop clinically significant iron overload, suggesting the importance of genetic modifiers. Murine hfe knockout models have demonstrated that strain background has a strong effect on the severity of iron loading. We noted that hepatic iron loading in hfe−/− mice occurs primarily over the first postnatal weeks (loading phase) followed by a timeframe of relatively static iron concentrations (plateau phase). We thus evaluated the effects of background strain and of age on hepatic gene expression in Hfe knockout mice (hfe−/−). Hepatic gene expression profiles were examined using cDNA microarrays in 4- and 8-week-old hfe−/− and wild-type mice on two different genetic backgrounds, C57BL/6J (C57) and AKR/J (AKR). Genes differentially regulated in all hfe−/− mice groups, compared with wild-type mice, including those involved in cell survival, stress and damage responses and lipid metabolism. AKR strain-specific changes in lipid metabolism genes and C57 strain-specific changes in cell adhesion and extracellular matrix protein genes were detected in hfe−/− mice. Mouse strain and age are each significantly associated with hepatic gene expression profiles in hfe−/− mice. These affects may underlie or reflect differences in iron loading in these mice.
AB - Hereditary hemochromatosis is an iron overload disorder most commonly caused by a defect in the HFE gene. While the genetic defect is highly prevalent, the majority of individuals do not develop clinically significant iron overload, suggesting the importance of genetic modifiers. Murine hfe knockout models have demonstrated that strain background has a strong effect on the severity of iron loading. We noted that hepatic iron loading in hfe−/− mice occurs primarily over the first postnatal weeks (loading phase) followed by a timeframe of relatively static iron concentrations (plateau phase). We thus evaluated the effects of background strain and of age on hepatic gene expression in Hfe knockout mice (hfe−/−). Hepatic gene expression profiles were examined using cDNA microarrays in 4- and 8-week-old hfe−/− and wild-type mice on two different genetic backgrounds, C57BL/6J (C57) and AKR/J (AKR). Genes differentially regulated in all hfe−/− mice groups, compared with wild-type mice, including those involved in cell survival, stress and damage responses and lipid metabolism. AKR strain-specific changes in lipid metabolism genes and C57 strain-specific changes in cell adhesion and extracellular matrix protein genes were detected in hfe−/− mice. Mouse strain and age are each significantly associated with hepatic gene expression profiles in hfe−/− mice. These affects may underlie or reflect differences in iron loading in these mice.
UR - http://www.scopus.com/inward/record.url?scp=84919951058&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84919951058&partnerID=8YFLogxK
U2 - 10.1007/s12263-014-0443-1
DO - 10.1007/s12263-014-0443-1
M3 - Article
AN - SCOPUS:84919951058
VL - 10
SP - 1
EP - 9
JO - Genes and Nutrition
JF - Genes and Nutrition
SN - 1555-8932
IS - 1
ER -