QTL for t-psl on Chr17 at Hp (53.97 Mbp , Build 37)
Description:
t-psl spans 28.97 - 78.97 Mbp (NCBI Build 37) on Chr17. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for METH responses for chewing on Chr17 at Hprt-ps1 (77.06 Mbp , Build 37)
Description:
METH responses for chewing spans 52.06 - 102.06 Mbp (NCBI Build 37) on Chr17. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Ethanol Induced Ataxia Chr#17 rs3672987(33247165) with right flanking marker rs4136382(3388912) and left marker rs3715723(58810428). This was mapped in 300 + (b6x129)F2 mice.
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists also possess anti-addictive characteristics. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated. We tested three PPAR agonists in a continuous access two-bottle choice (2BC) drinking paradigm and found that tesaglitazar (PPARα/γ; 1.5 mg/kg) and fenofibrate (PPARα; 150 mg/kg) decreased ethanol consumption in male C57BL/6J mice while bezafibrate (PPARα/γ/β; 75 mg/kg) did not. We hypothesized that changes in brain gene expression following fenofibrate and tesaglitazar treatment lead to reduced ethanol drinking. We studied unbiased genomic profiles in areas of the brain known to be important for ethanol dependence, the prefrontal cortex (PFC) and amygdala, and also profiled gene expression in liver. Genomic profiles from the non-effective bezafibrate treatment were used to filter out genes not associated with ethanol consumption. Because PPAR agonists are anti-inflammatory, they would be expected to target microglia and astrocytes. Surprisingly, PPAR agonists produced a strong neuronal signature in mouse brain, and fenofibrate and tesaglitazar (but not bezafibrate) targeted a subset of GABAergic interneurons in the amygdala. Weighted gene co-expression network analysis (WGCNA) revealed co-expression of treatment-significant genes. Functional annotation of these gene networks suggested that PPAR agonists might act via neuropeptide and dopaminergic signaling pathways in the amygdala. Our results reveal gene targets through which PPAR agonists can affect alcohol consumption behavior.
Authors:
Laura B Ferguson, Dana Most, Yuri A Blednov, R Adron Harris
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists also possess anti-addictive characteristics. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated. We tested three PPAR agonists in a continuous access two-bottle choice (2BC) drinking paradigm and found that tesaglitazar (PPARα/γ; 1.5 mg/kg) and fenofibrate (PPARα; 150 mg/kg) decreased ethanol consumption in male C57BL/6J mice while bezafibrate (PPARα/γ/β; 75 mg/kg) did not. We hypothesized that changes in brain gene expression following fenofibrate and tesaglitazar treatment lead to reduced ethanol drinking. We studied unbiased genomic profiles in areas of the brain known to be important for ethanol dependence, the prefrontal cortex (PFC) and amygdala, and also profiled gene expression in liver. Genomic profiles from the non-effective bezafibrate treatment were used to filter out genes not associated with ethanol consumption. Because PPAR agonists are anti-inflammatory, they would be expected to target microglia and astrocytes. Surprisingly, PPAR agonists produced a strong neuronal signature in mouse brain, and fenofibrate and tesaglitazar (but not bezafibrate) targeted a subset of GABAergic interneurons in the amygdala. Weighted gene co-expression network analysis (WGCNA) revealed co-expression of treatment-significant genes. Functional annotation of these gene networks suggested that PPAR agonists might act via neuropeptide and dopaminergic signaling pathways in the amygdala. Our results reveal gene targets through which PPAR agonists can affect alcohol consumption behavior.
Authors:
Laura B Ferguson, Dana Most, Yuri A Blednov, R Adron Harris
QTL for differences in cocaine responsiveness on Chr17 at Ck-2 (45.25 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 20.25 - 70.25 Mbp (NCBI Build 37) on Chr17. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for differences in cocaine responsiveness on Chr17 at D17MIt7 (51.99 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 26.99 - 76.99 Mbp (NCBI Build 37) on Chr17. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL associated with Angiostrongylus costaricensis nematode susceptibility 3. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (34380179)
QTL associated with adenovirus induced hyperthyroidism 2. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (47859524)
Authors:
Aliesky HA, Pichurin PN, Chen CR, Williams RW, Rapoport B, McLachlan SM
QTL associated with antibody response to human factor IX. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (33874679)
QTL associated with B.burgdorferi-associated arthritis 8. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (37346853)
QTL associated with bleomycin pulmonary fibrosis 1. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (35216590)
QTL associated with P. chabaudi malaria resistance QTL 3. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (34380179)
Authors:
Longley R, Smith C, Fortin A, Berghout J, McMorran B, Burgio G, Foote S, Gros P
QTL associated with P. chabaudi malaria resistance QTL 7. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (55545184)
Authors:
Longley R, Smith C, Fortin A, Berghout J, McMorran B, Burgio G, Foote S, Gros P
QTL associated with cerebral malaria susceptibility in CBA/N. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (34137861)
QTL associated with cocaine induced activation 13. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (47859524)
QTL associated with CD86 expression in activated macrophages. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (57366870)
Authors:
Karlsson J, Johannesson M, Lindvall T, Wernhoff P, Holmdahl R, Andersson A
QTL associated with delta power in slow-wave sleep 3. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (34137861)
QTL associated with experimental allergic encephalomyelitis susceptibility 5. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (41438808)
Authors:
Teuscher C, Doerge RW, Fillmore PD, Blankenhorn EP
QTL associated with early growth adjusted QTL 2. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (41935172)
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