Abstract
Interactions between genetic and early environmental factors are recognized to play a critical role in modulating susceptibility to disease, particularly mental illness. In order to better understand such mechanisms at the molecular level, we have developed a screening paradigm in mice that allows us to test the ability of targeted mutations in candidate genes to modify susceptibility to the long-term effects of different maternal environment. Offspring of genetically identical F1 hybrid dams produced by reciprocal breeding of C57BL/6 and BALB/c parents show alterations in anxiety-related behavior as a consequence of their different maternal environment. Introduction of targeted mutations into these offspring via the father allows for the identification of candidate genes that alter these maternal effects. Our strategy offers several advantages over other methods to study maternal effects, including the use of genetically identical parents, the ability to identify both prenatal and postnatal effects, the straightforward introduction of mutations and its adaptability to high-throughput screening. In order to test the utility of this paradigm to screen candidate genes, we tested for gene-environment interactions involving loss-of-function mutations in the serotonin 1A receptor gene. Our studies demonstrate that early gene-environment interactions can be successfully tested in the mouse. When combined with conditional gene targeting and other molecular genetic techniques available in the mouse, this approach has the potential to identify the molecular mechanisms underlying early gene-environment effects.
| Original language | English |
|---|---|
| Pages (from-to) | 189-199 |
| Number of pages | 11 |
| Journal | Genes, Brain and Behavior |
| Volume | 5 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Mar 2006 |
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Keywords
- Anxiety
- Gene targeting
- GPCR
- Maternal environment
- Mice
- Serotonin
ASJC Scopus subject areas
- Neuroscience(all)
- Genetics
Cite this
Identifying interactions between genes and early environment in the mouse. / Carola, V.; Frazzetto, G.; Gross, C.
In: Genes, Brain and Behavior, Vol. 5, No. 2, 03.2006, p. 189-199.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Identifying interactions between genes and early environment in the mouse
AU - Carola, V.
AU - Frazzetto, G.
AU - Gross, C.
PY - 2006/3
Y1 - 2006/3
N2 - Interactions between genetic and early environmental factors are recognized to play a critical role in modulating susceptibility to disease, particularly mental illness. In order to better understand such mechanisms at the molecular level, we have developed a screening paradigm in mice that allows us to test the ability of targeted mutations in candidate genes to modify susceptibility to the long-term effects of different maternal environment. Offspring of genetically identical F1 hybrid dams produced by reciprocal breeding of C57BL/6 and BALB/c parents show alterations in anxiety-related behavior as a consequence of their different maternal environment. Introduction of targeted mutations into these offspring via the father allows for the identification of candidate genes that alter these maternal effects. Our strategy offers several advantages over other methods to study maternal effects, including the use of genetically identical parents, the ability to identify both prenatal and postnatal effects, the straightforward introduction of mutations and its adaptability to high-throughput screening. In order to test the utility of this paradigm to screen candidate genes, we tested for gene-environment interactions involving loss-of-function mutations in the serotonin 1A receptor gene. Our studies demonstrate that early gene-environment interactions can be successfully tested in the mouse. When combined with conditional gene targeting and other molecular genetic techniques available in the mouse, this approach has the potential to identify the molecular mechanisms underlying early gene-environment effects.
AB - Interactions between genetic and early environmental factors are recognized to play a critical role in modulating susceptibility to disease, particularly mental illness. In order to better understand such mechanisms at the molecular level, we have developed a screening paradigm in mice that allows us to test the ability of targeted mutations in candidate genes to modify susceptibility to the long-term effects of different maternal environment. Offspring of genetically identical F1 hybrid dams produced by reciprocal breeding of C57BL/6 and BALB/c parents show alterations in anxiety-related behavior as a consequence of their different maternal environment. Introduction of targeted mutations into these offspring via the father allows for the identification of candidate genes that alter these maternal effects. Our strategy offers several advantages over other methods to study maternal effects, including the use of genetically identical parents, the ability to identify both prenatal and postnatal effects, the straightforward introduction of mutations and its adaptability to high-throughput screening. In order to test the utility of this paradigm to screen candidate genes, we tested for gene-environment interactions involving loss-of-function mutations in the serotonin 1A receptor gene. Our studies demonstrate that early gene-environment interactions can be successfully tested in the mouse. When combined with conditional gene targeting and other molecular genetic techniques available in the mouse, this approach has the potential to identify the molecular mechanisms underlying early gene-environment effects.
KW - Anxiety
KW - Gene targeting
KW - GPCR
KW - Maternal environment
KW - Mice
KW - Serotonin
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UR - http://www.scopus.com/inward/citedby.url?scp=33644749610&partnerID=8YFLogxK
U2 - 10.1111/j.1601-183X.2005.00152.x
DO - 10.1111/j.1601-183X.2005.00152.x
M3 - Article
C2 - 16507009
AN - SCOPUS:33644749610
VL - 5
SP - 189
EP - 199
JO - Genes, Brain and Behavior
JF - Genes, Brain and Behavior
SN - 1601-1848
IS - 2
ER -