Influence of ethanol on thermoregulation: mapping quantitative trait loci

2001 ◽  
Vol 7 (2) ◽  
pp. 159-169 ◽  
Author(s):  
LARRY I. CRAWSHAW ◽  
HELEN L. WALLACE ◽  
ROBIN CHRISTENSEN ◽  
JOHN C. CRABBE

The genetic basis for the effects of ethanol on thermoregulation was investigated by utilizing recombinant inbred mouse strains from C57BL/6J and DBA/2J progenitor strains. Changes in core body temperature (Tc) and the degree of fluctuation of Tc were monitored in male mice following the administration of ethanol in an environment with cyclic changes in ambient temperature (Ta). Changes in Tc were utilized to assess ethanol-induced effects on regulated Tc, whereas fluctuations in Tc were utilized to assess thermoregulatory disruption. Ethanol was administered intraperitoneally at 1.5, 2.5, and 3.5 g/kg for all strains. Change in Tc and increase in tail temperature were also evaluated at 2.5 g/kg ethanol in a constant Ta of 26°C. Associations between the measured physiological responses and previously mapped genetic markers were used to identify quantitative trait loci (QTLs). This established probable chromosome locations for a number of genes for the responses. To our knowledge, this is the first report of QTLs that underlie changes in regulation as well as the disruption of a physiological regulatory system.

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 919-926 ◽  
Author(s):  
Edward H. Leiter ◽  
Peter C. Reifsnyder ◽  
Weidong Zhang ◽  
Huei-ju Pan ◽  
Qiang Xiao ◽  
...  

Polygenic mouse models for obesity-induced type 2 diabetes (T2D) more accurately reflect the most common manifestations of the human disease. Two inbred mouse strains (NON/Lt and NZO/HlLt) separately contributed T2D susceptibility- conferring quantitative trait loci to F1 males. Although chronic administration of rosiglitazone (Rosi) in diet (50 mg/kg) effectively suppressed F1 diabetes, hepatosteatosis was an undesired side effect. Three recombinant congenic strains (designated RCS1, -2, and -10) developed on the NON/Lt background carry variable numbers of these quantitative trait loci that elicit differential weight gain and male glucose intolerance syndromes of variable severity. We previously showed that RCS1 and -2 mice responded to chronic Rosi therapy without severe steatosis, whereas RCS10 males were moderately sensitive. In contrast, another recombinant congenic strain, RCS8, responded to Rosi therapy with the extreme hepatosteatosis observed in the F1. Longitudinal changes in multiple plasma analytes, including insulin, the adipokines leptin, resistin, and adiponectin, and plasminogen activator inhibitor-1 (PAI-1) allowed profiling of the differential Rosi responses in steatosis-exacerbated F1 and RCS8 males vs. the resistant RCS1 and RCS2 or moderately sensitive RCS10. Of these biomarkers, PAI-1 most effectively predicted adverse drug responses. Unexpectedly, mean resistin concentrations were higher in Rosi-treated RCS8 and RCS10. In summary, longitudinal profiling of multiple plasma analytes identified PAI-1 as a useful biomarker to monitor for differential pharmacogenetic responses to Rosi in these new mouse models of T2D.


1997 ◽  
Vol 17 (2) ◽  
pp. 745-754 ◽  
Author(s):  
Judith E. Grisel ◽  
John K. Belknap ◽  
L. A. O’Toole ◽  
M. L. Helms ◽  
Charlotte D. Wenger ◽  
...  

Genetics ◽  
2002 ◽  
Vol 162 (3) ◽  
pp. 1341-1353 ◽  
Author(s):  
Andréa C Peripato ◽  
Reinaldo A de Brito ◽  
Ty T Vaughn ◽  
L Susan Pletscher ◽  
Sergio R Matioli ◽  
...  

Abstract Maternal performance refers to the effect that the environment provided by mothers has on their offspring’s phenotypes, such as offspring survival and growth. Variations in maternal behavior and physiology are responsible for variations in maternal performance, which in turn affects offspring survival. In our study we found females that failed to nurture their offspring and showed abnormal maternal behaviors. The genetic architecture of maternal performance for offspring survival was investigated in 241 females of an F2 intercross of the SM/J and LG/J inbred mouse strains. Using interval-mapping methods we found two quantitative trait loci (QTL) affecting maternal performance at D2Mit17 + 6 cM and D7Mit21 + 2 cM on chromosomes 2 and 7, respectively. In a two-way genome-wide epistasis scan we found 15 epistatic interactions involving 23 QTL distributed across all chromosomes except 12, 16, and 17. These loci form several small sets of interacting QTL, suggesting a complex set of mechanisms operating to determine maternal performance for offspring survival. Taken all together and correcting for the large number of significant factors, QTL and their interactions explain almost 35% of the phenotypic variation for maternal performance for offspring survival in this cross. This study allowed the identification of many possible candidate genes, as well as the relative size of gene effects and patterns of gene action affecting maternal performance in mice. Detailed behavior observation of mothers from later generations suggests that offspring survival in the first week is related to maternal success in building nests, grooming their pups, providing milk, and/or manifesting aggressive behavior against intruders.


2010 ◽  
Vol 283 (4) ◽  
pp. 317-326 ◽  
Author(s):  
Adriana S. Leme ◽  
Annerose Berndt ◽  
Laura K. Williams ◽  
Shirng-Wern Tsaih ◽  
Jin P. Szatkiewicz ◽  
...  

1994 ◽  
Vol 7 (1) ◽  
pp. 54-58 ◽  
Author(s):  
Wade H. Berrettini ◽  
Thomas N. Ferraro ◽  
Robert C. Alexander ◽  
Arthur M. Buchberg ◽  
Wolfgang H. Vogel

Blood ◽  
2002 ◽  
Vol 99 (2) ◽  
pp. 561-566 ◽  
Author(s):  
Jichun Chen ◽  
David E. Harrison

Abstract Relative proportions of peripheral blood (PB) B lymphocytes (B220%) as well as CD4 (CD4%) and CD8 (CD8%) T lymphocytes differ significantly among inbred mouse strains: B220% is high in C57BL/6J (B6) and C57BR/cdJ, intermediate in BALB/cByJ (BALB) and DBA/2J (D2), and low in NOD/LtJ (NOD) and SJL/J (SJL) mice, whereas CD4% and CD8% are high in NOD and SJL mice and low in the other 4 strains. By following segregating genetic markers linked to these traits in (B6 × D2) recombinant inbred (BXD RI) mice, the study defined 2 quantitative trait loci (QTLs) for the B220% phenotype:Pbbcp1 (peripheral blood B cell percentage 1, logarithm of odds [LOD] 4.1, P < .000 01) and Pbbcp2(LOD 3.7, P < .000 04) on chromosome 1 (Chr 1) at about 63 cM and 48 cM; one suggestive locus for the CD4% phenotype (LOD 2.6,P < .000 57) on Chr 8 at about 73 cM; and one QTL for the CD8% phenotype: Pbctlp1 (peripheral blood cytotoxic T lymphocyte percentage 1, LOD 3.8, P < .000 02) on Chr 19 at about 12 cM. The study further segregated PB lymphocyte proportions in B6SJLF2 mice by using DNA markers adjacent to these mapped QTLs and found that the Pbbcp1 locus (LOD 5.6,P < .000 01) was also important in this mouse population. In both BXD RI and B6SJLF2 mice, QTLs regulating B-cell proportions showed no significant effect on T-cell proportions and vice versa. Thus, PB B- and T-lymphocyte proportions are regulated separately by different genetic elements.


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