scholarly journals Strain survey and genetic analysis of vasoreactivity in mouse aorta

2016 ◽  
Vol 48 (11) ◽  
pp. 861-873 ◽  
Author(s):  
Seung Kyum Kim ◽  
Joshua J. Avila ◽  
Michael P. Massett
Keyword(s):  
Endothelial Function ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Large Strain ◽  
Inbred Mouse ◽  
Strain Differences ◽  
Mouse Strains ◽  
Response Curves ◽  
Significant Locus ◽  
Genetically Determined

Understanding the genetic influence on vascular reactivity is important for identifying genes underlying impaired vascular function. The purpose of this study was to characterize the genetic contribution to intrinsic vascular function and to identify loci associated with phenotypic variation in vascular reactivity in mice. Concentration response curves to phenylephrine (PE), potassium chloride (KCl), acetylcholine (ACh), and sodium nitroprusside (SNP) were generated in aortic rings from male mice (12 wk old) from 27 inbred mouse strains. Significant strain-dependent differences were found for both maximal responses and sensitivity for each agent, except for SNP Max (%). Strain differences for maximal responses to ACh, PE, and KCl varied by two- to fivefold. On the basis of these large strain differences, we performed genome-wide association mapping (GWAS) to identify loci associated with variation in responses to these agents. GWAS for responses to ACh identified four significant and 19 suggestive loci. Several suggestive loci for responses to SNP, PE, and KCl (including one significant locus for KCl EC50) were also identified. These results demonstrate that intrinsic endothelial function, and more generally vascular function, is genetically determined and associated with multiple genomic loci. Furthermore, these results are supported by the finding that several genes residing in significant and suggestive loci for responses to ACh were previously identified in rat and/or human quantitative trait loci/GWAS for cardiovascular disease. This study represents the first step toward the unbiased comprehensive discovery of genetic determinants that regulate intrinsic vascular function, particularly endothelial function.

scholarly journals Acute Effects of Triiodothyronine on Endothelial Function in Human Subjects

2007 ◽  
Vol 92 (1) ◽  
pp. 250-254 ◽  
Author(s):  
Raffaele Napoli ◽  
Vincenzo Guardasole ◽  
Valentina Angelini ◽  
Emanuela Zarra ◽  
Daniela Terracciano ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Dose Response ◽  
Vascular Reactivity ◽  
Controlled Trial ◽  
University Hospital ◽  
Acute Effects ◽  
Response Curves ◽  
Double Blind ◽  
Low T3 ◽  
Dose Response Curves

Abstract Context: Thyroid hormone regulates several cardiovascular functions, and low T3 levels are frequently associated with cardiovascular diseases. Whether T3 exerts any acute and direct effect on endothelial function in humans is unknown. Objective: Our objective was to clarify whether acute changes in serum T3 concentration affect endothelial function. Design, Setting, and Subjects: Ten healthy subjects (age, 24 ± 1 yr) participated in a double-blind, placebo-controlled trial at a university hospital. Interventions: T3 (or placebo) was infused for 7 h into the brachial artery to raise local T3 to levels observed in moderate hyperthyroidism. Vascular reactivity was tested by intraarterial infusion of vasoactive agents. Main Outcome Measures: We assessed changes in forearm blood flow (FBF) measured by plethysmography. Results: FBF response to the endothelium-dependent vasodilator acetylcholine was enhanced by T3 (P = 0.002 for the interaction between T3 and acetylcholine). The slopes of the dose-response curves were 0.41 ± 0.06 and 0.23 ± 0.04 ml/dl·min/μg in the T3 and placebo study, respectively (P = 0.03). T3 infusion had no effect on the FBF response to sodium nitroprusside. T3 potentiated the vasoconstrictor response to norepinephrine (P = 0.006 for the interaction). Also, the slopes of the dose-response curves were affected by T3 (1.95 ± 0.77 and 3.83 ± 0.35 ml/dl·min/mg in the placebo and T3 study, respectively; P < 0.05). The increase in basal FBF induced by T3 was inhibited by NG-monomethyl-l-arginine. Conclusions: T3 exerts direct and acute effects on the resistance vessels by enhancing endothelial function and norepinephrine-induced vasoconstriction. The data may help clarify the vascular impact of the low T3 syndrome and point to potential therapeutic strategies.

scholarly journals Strain Differences in the Morphology of the Gametes of the Mouse

1959 ◽  
Vol 12 (1) ◽  
pp. 65 ◽  
Author(s):  
AWH Braden
Keyword(s):  
Inbred Mouse ◽  
Strain Differences ◽  
Sperm Head ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Posterior Portion ◽  
Interstrain Differences

Characteristic differences in the morphology of the spenTI head have been noted between. the inbred mouse strains C57BL, CBA, A, and RIlL There were interstrain differences in the shape of the posterior portion of the sperm head and in the length and width of the .head. The spenTI of mice derived from certain interstrain crosses were also studied.

Genetic variability in forced and voluntary endurance exercise performance in seven inbred mouse strains

2002 ◽  
Vol 92 (6) ◽  
pp. 2245-2255 ◽  
Author(s):  
Imanuel Lerman ◽  
Brooke C. Harrison ◽  
Kalev Freeman ◽  
Timothy E. Hewett ◽  
David L. Allen ◽  
...  
Keyword(s):  
Exercise Performance ◽  
Treadmill Exercise ◽  
Inbred Mouse ◽  
Cardiac Contractility ◽  
Strain Differences ◽  
Voluntary Exercise ◽  
Mouse Strains ◽  
Apparent Relationship ◽  
Molecular Indicators ◽  
Voluntary Wheel

The goal of this study was to characterize the genetic contribution to both forced and voluntary exercise performance and to determine whether performance in these two paradigms is controlled by similar genetic influences. There were marked strain differences in treadmill exercise performance, with Swiss Webster (SW) and FVB/NJ mice showing elevated performance and C57BL/6J animals showing decreased performance compared with all other strains. There was no apparent relationship between treadmill performance and voluntary wheel performance, with the exception of SW mice, which demonstrated high performances on both the treadmill and the voluntary wheel. Numerous properties were measured to attempt to understand the basis for these differences in exercise performance. DBA/1J and SW mice exhibited significantly greater cardiac contractility than all other analyzed strains. Conversely, BALB/cByJ mice exhibited significantly reduced cardiac contractility compared with all other strains. Expression of molecular indicators of hypertrophy (atrial natriuretic factor and β-myosin heavy chain) was significantly elevated in DBA/2J myocardium compared with all other analyzed strains.

scholarly journals Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis

1998 ◽  
Vol 274 (3) ◽  
pp. G544-G551 ◽  
Author(s):  
Michael Mähler ◽  
Ian J. Bristol ◽  
Edward H. Leiter ◽  
Aletha E. Workman ◽  
Edward H. Birkenmeier ◽  
...  
Keyword(s):  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Inbred Mouse ◽  
Strain Differences ◽  
Nod Mice ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Anatomical Site ◽  
Inbred Strains Of Mice ◽  
Mhc Haplotype

Dextran sulfate sodium (DSS)-induced murine colitis represents an experimental model for human inflammatory bowel disease. The aim of this study was to screen various inbred strains of mice for genetically determined differences in susceptibility to DSS-induced colitis. Mice of strains C3H/HeJ, C3H/HeJBir, C57BL/6J, DBA/2J, NOD/LtJ, NOD/LtSz- Prkdcscid/Prkdcscid , 129/SvPas, NON/LtJ, and NON.NOD- H2g7 were fed 3.5% DSS in drinking water for 5 days and necropsied 16 days later. Ceca and colons were scored for histological lesions based on severity, ulceration, hyperplasia, and area involved. Image analysis was used to quantitate the proportion of cecum ulcerated. Histological examination revealed significant differences among inbred strains for all parameters scored. In both cecum and colon, C3H/HeJ and a recently selected substrain, C3H/HeJBir, were highly DSS susceptible. NOD/LtJ, an autoimmune-prone strain, and NOD/LtSz- Prkdcscid/Prkdcscid , a stock with multiple defects in innate and adoptive immunity, were also highly DSS susceptible. NON/LtJ, a strain closely related to NOD, was quite DSS resistant. The major histocompatibility (MHC) haplotype of NOD mice ( H2g7 ), a major component of the NOD autoimmune susceptibility, was not crucial in determining DSS susceptibility, since NON mice congenic for this MHC haplotype retained resistance. C57BL/6J, 129/SvPas, and DBA/2J mice showed various degrees of susceptibility, depending upon the anatomical site. A greater male susceptibility to DSS-induced colonic but not cecal lesions was observed. In summary, this study demonstrates major differences in genetic susceptibility to DSS-induced colitis among inbred strains of mice. Knowledge of these strain differences in genetic responsiveness to acute inflammatory stress in the large intestine will permit design of genetic crosses to elucidate the genes involved.

scholarly journals Disrupted Endothelial Cell Heterogeneity and Network Organization Impairs Vascular Function in Prediabetic Obesity

2020 ◽  
Author(s):  
Calum Wilson ◽  
Xun Zhang ◽  
Matthew D. Lee ◽  
Margaret MacDonald ◽  
Helen H. Heathcote ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Cells ◽  
Endothelial Function ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Single Photon ◽  
Hexagonal Lattice ◽  
Network Organization ◽  
Cell Heterogeneity ◽  
Functional Components

AbstractRationaleObesity is a major risk factor for diabetes and cardiovascular diseases such as hypertension, heart failure, and stroke. Impaired endothelial function occurs in the earliest stages of obesity and underlies vascular alterations giving rise to cardiovascular disease. However, the mechanisms that link weight gain to endothelial dysfunction are ill-defined. Increasing evidence suggests that, rather than being a population of uniformly responding cells, neighboring endothelial cells are highly heterogeneous and are organized as a communicating multicellular network that controls vascular function.ObjectiveTo investigate the hypothesis that disrupted endothelial heterogeneity and network-level organization contributes to impaired vascular reactivity in obesity.Methods and ResultsTo study obesity-related vascular function without the complications associated with diabetes, we induced a state of prediabetic obesity in rats. Small artery diameter recordings confirmed nitric-oxide mediated vasodilator responses were dependent on increases in endothelial calcium levels and were impaired in obese animals. Single-photon imaging revealed a linear relationship between blood vessel relaxation and network-level calcium responses. Obesity did not alter the slope of this relationship, but impaired network-level endothelial calcium responses. The network itself was comprised of structural and functional components. The structural component, a hexagonal lattice network of endothelial cells, was unchanged in obesity. The functional network contained sub-populations of clustered agonist-sensing cells from which signals were communicate through the network. In obesity there were fewer but larger clusters of agonist-sensing cells and communication path lengths between clusters was increased. Communication between neighboring cells was unaltered in obesity. Altered network organization resulted in impaired, population-level calcium signaling and deficient endothelial control of vascular tone.Specialized subpopulations of endothelial cells had increased agonist sensitivity. These agonist-responsive cells were spatially clustered in a non-random manner and drove network level calcium responses. Communication between adjacent cells was unaltered in obesity, but there was a decrease in the size of the agonist-sensitive cell population and an increase in the clustering of agonist-responsive cellsConclusionsThe distribution of cells in the endothelial network is critical in determining overall vascular function. Altered cell heterogeneity and arrangement in obesity decrease endothelial function and provide a novel framework for understanding compromised endothelial function in cardiovascular disease.

Influence of Nociception and Stress-induced Antinociception on Genetic Variation in Isoflurane Anesthetic Potency among Mouse Strains

2005 ◽  
Vol 103 (4) ◽  
pp. 751-758 ◽  
Author(s):  
Jeffrey S. Mogil ◽  
Shad B. Smith ◽  
Meghan K. O'Reilly ◽  
Gilles Plourde
Keyword(s):  
Genetic Variability ◽  
Inbred Mouse ◽  
Strain Differences ◽  
Mouse Strains ◽  
Noxious Stimulation ◽  
Baseline Sensitivity ◽  
Nociceptive Sensitivity ◽  
Righting Response ◽  
Anesthetic Potency ◽  
Tail Clip

Background Genetic background influences anesthetic potency to suppress motor response to noxious stimulation (minimum alveolar concentration [MAC]) as well as nociceptive sensitivity in unmedicated animals. However, the influence on MAC of baseline sensitivity to the noxious stimuli used to assess MAC has virtually never been studied. The authors assessed room air nociceptive sensitivity and isoflurane MAC in multiple mouse strains. Isoflurane requirement for loss of righting response (MACLORR) was also measured. Methods One outbred and 10 inbred mouse strains were tested for latency to respond (in room air) to a tail clip (either 500 g or 2,000 g). Naive mice of the same 11 strains were tested for isoflurane MAC and MACLORR. To assess the role of opioid-mediated stress-induced antinociception, mice were also tested for nociceptive sensitivity after injection of naloxone (10 mg/kg) or saline. Results Robust strain differences were observed for all measures. The authors found that tail-clip latency (using a 500-g or 2,000-g clip, respectively) correlated significantly with MAC (r = -0.76 and -0.58, respectively) but not MACLORR (r = -0.10 and -0.26). Naloxone produced strain-dependent reductions in open air tail-clip latencies, and these reductions were also strongly correlated with MAC (r = -0.67 and -0.71). Conclusions The authors suggest that genetic variability in isoflurane MAC (but not MACLORR) may reflect genetic variability in the underlying sensitivity to the noxious stimulus being used to measure MAC. This variable sensitivity to nociception in the awake state is at least partially mediated by endogenous antinociceptive mechanisms activated by the tail-clip stimulus itself.

scholarly journals Genetic Relationships Between Ethanol-Induced Conditioned Place Aversion and Other Ethanol Phenotypes in 15 Inbred Mouse Strains

2019 ◽  
Vol 9 (8) ◽  
pp. 209 ◽  
Author(s):  
Christopher L. Cunningham
Keyword(s):  
Genetic Relationships ◽  
Inbred Mouse ◽  
Genetic Correlations ◽  
Strain Differences ◽  
Mouse Strains ◽  
Place Conditioning ◽  
Conditioned Place Aversion ◽  
Inbred Mouse Strains ◽  
Place Aversion ◽  
Tactile Cues

The genetic relationships between different behaviors used to index the aversive effects of ethanol are unknown. To address this issue, ethanol-induced conditioned place aversion (CPA) was tested in a genetically diverse panel of 15 inbred mouse strains. Mice were exposed to an unbiased place conditioning procedure using ethanol doses of 0, 2, or 4 g/kg; all injections were given immediately after 5-min exposure to distinctive tactile cues. There were dose-dependent effects of ethanol on CPA and on the change in pre-injection activity rates between the first and last conditioning trials. Most strains (80%) developed CPA, demonstrating the generalizability of this behavior. Moreover, genotype had significant effects on CPA magnitude and locomotor activity rates. Strain means from this study and previously published studies were then used to examine genetic correlations. These analyses showed significant genetic correlations between CPA and ethanol intake/preference, conditioned taste aversion, and drug withdrawal (but not blood ethanol concentration or conditioned place preference), supporting the idea of commonality in the genes underlying CPA and each of these behaviors. The overall pattern of findings is consistent with previous data suggesting that genetic differences in sensitivity to ethanol’s aversive effects play a role in determining strain differences in ethanol drinking. The broader implication is that individuals who are more sensitive to the aversive effects of ethanol may be protected from developing the excessive drinking behaviors characteristic of alcohol use disorders.

Genetic strain differences in platelet aggregation of laboratory mice

2006 ◽  
Vol 95 (01) ◽  
pp. 159-165 ◽  
Author(s):  
Hideki Ito ◽  
Yukio Kimura ◽  
Toshiki Sudo
Keyword(s):  
Platelet Aggregation ◽  
Knockout Mice ◽  
Strain Difference ◽  
Inbred Mouse ◽  
Laboratory Mouse ◽  
Physiological Role ◽  
Strain Differences ◽  
Mouse Strains ◽  
Laboratory Mice

SummaryTo investigate the physiological role of novel genes and proteins in platelet activation, various knockout mice have been produced. A number of standard inbred mouse strains each possessing genetically unique characters such as high tumor generation, hyperglycemia or hyperlipidemia, have been bred. In breeding knockout mice for investigation of specific physiological functions, appropriate selection of parental or backcross strains is necessary. Thus, examination of strain-specific platelet characteristics is important. In the present study, platelet aggregation responses of 13 laboratory mouse strains, 129/Sv, A, AKR, BALB/c, C3H/He, C57BL/6J, CBA, DBA/1, DBA/2, ddY, FVB, ICR, and NZW, and the diabetic strain C57BL/KsJ db/db, were compared. Marked strain differences were observed inADP- and collagen-induced platelet aggregation. The highest responses with both were seen in AKR/J and NZW/N, whereas the lowest were seen in DBA/2 and DBA/1.There was a 5-fold difference in the platelet aggregation threshold index (PATI) for ADP-induced PRP aggregation between AKR/J (0.6 µM) and DBA/2 (3.0 µM). With whole blood aggregation, the highest response was seen in AKR, whereas the lowest was seen in DBA/2 and DBA/1. The present study demonstrated that there is considerable strain difference in platelet aggregation among laboratory mice, which should be taken into account in backcrossing knockout strains.

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