Characteristics of the aortic elastic network and related phenotypes in seven inbred rat strains

2005 ◽  
Vol 288 (2) ◽  
pp. H769-H777 ◽  
Author(s):  
Jacques Behmoaras ◽  
Mary Osborne-Pellegrin ◽  
Dominique Gauguier ◽  
Marie-Paule Jacob

Extracellular matrix (ECM) molecules such as elastin and collagen provide mechanical support to the vessel wall and are essential for vascular function. Evidence that genetic factors influence aortic ECM composition and organization was concluded from our previous studies showing that the inbred Brown Norway (BN) rat differs significantly from the outbred Long-Evans (LE) and the inbred LOU rat with respect to both thoracic aortic elastin content and internal elastic lamina (IEL) rupture in the abdominal aorta and iliac arteries. Here, we measured aortic elastin and collagen contents as well as factors that may modulate these parameters [insulin growth factor (IGF)-I, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)-2] in seven inbred rat strains, including BN and LOU. We also investigated whether IEL ruptures occur in strains other than BN. We showed that LOU, LE, BN, and Fischer 344 (F344) rats were significantly different for aortic elastin content and elastin-to-collagen ratio, whereas LE, Lewis, WAG, and Wistar-Furth (WF) were similar for these parameters. BN and F344 had the lowest values. BN was the only strain to present numerous IEL ruptures, whereas F344, LE, and WF presented a few and the other strains presented none. In addition, IGF-I and TGF-β1 levels in the plasma and aorta differed significantly between strains, suggesting genetic control of their production. Because inbred rat strains provide interesting models for quantitative trait locus analysis, our results concerning elastin, collagen, IEL ruptures, and cytokines may provide a basis for the search for candidate genes involved in the control of these phenotypes.

2018 ◽  
Author(s):  
Shweta Ramdas ◽  
Ayse Bilge Ozel ◽  
Mary K. Treutelaar ◽  
Katie Holl ◽  
Myrna Mandel ◽  
...  

AbstractWe performed whole-genome sequencing for eight inbred rat strains commonly used in genetic mapping studies. They are the founders of the NIH heterogeneous stock (HS) outbred colony. We provide their sequences and variant calls to the rat genomics community. When analyzing the variant calls we identified regions with unusually high levels of heterozygosity. These regions are consistent across the eight inbred strains, including Brown Norway, which is the basis of the rat reference genome. These regions show higher read depths than other regions in the genome and contain higher rates of apparent tri-allelic variant sites. The evidence suggests that these regions may correspond to duplicated segments that were incorrectly overlaid as a single segment in the reference genome. We provide masks for these regions of suspected mis-assembly as a resource for the community to flag potentially false interpretations of mapping or functional results.


1998 ◽  
Vol 274 (2) ◽  
pp. R420-R427 ◽  
Author(s):  
Francisca Gómez ◽  
E. Ronald De Kloet ◽  
Antonio Armario

The aim of the present work was to study the influence of altering glucocorticoid negative feedback on both basal activity of the hypothalamic-pituitary-adrenal (HPA) axis and its response to acute stress (tail shock) in five inbred rat strains known to differ in some depression-like behaviors: Brown Norway (BN), Fischer 344 (F344), Lewis (Lew), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY) rats. Two complementary approaches were used: 1) enhancement of negative feedback by administration of 0.05 and 0.2 mg/kg dexamethasone (Dex) and 2) attenuation of negative feedback by pharmacological adrenalectomy (PhADX). The results indicate that 1) Lew rats consistently show adrenocorticotropic hormone (ACTH) and corticosterone hyporesponsiveness to stress, 2) interstrain differences in the effect of Dex on the HPA axis were very weak and not related apparently to differences in the metabolism of the steroid, 3) the suppressive effect of the highest dose of Dex on basal corticosterone levels was lower in BN rats than in the other strains, and 4) after PhADX, an increase in ACTH levels was observed in response to acute stress in BN, F344, and WKY but not in Lew and SHR rats, suggesting possible interstrain differences in pituitary sensitivity to neural stimuli induced by stress. In summary, our results indicate that there are differences among the strains with regard to both 1) the suppressive effect of Dex on the HPA axis, BN rats showing a certain degree of resistance, and 2) the capability of PhADX rats to respond to acute stress, which suggests a defective release of ACTH in Lew and SHR rats. The biological meaning of these alterations of corticosteroid negative feedback among the five inbred strains studied remains to be established.


2011 ◽  
Vol 43 (12) ◽  
pp. 758-765 ◽  
Author(s):  
Harold G. Klemcke ◽  
Bina Joe ◽  
Mariam L. Calderon ◽  
Rajiv Rose ◽  
Thomas Oh ◽  
...  

To find a genetic basis for differential ability to survive severe hemorrhage, we previously showed eightfold differences in survival times among inbred rat strains. We assumed that rat strains had similar normalized blood volumes (NBV; ml/100 g body wt). As NBV might vary among strains and constitute one genetic variable affecting survival time to hemorrhage, in experiment 1 of the current studies we first measured total blood volumes and calculated NBV in specific inbred rat strains (Brown Norway/Medical College of Wisconsin, BN; Dark Agouti, DA; Fawn Hooded Hypertensive, FHH; Lewis, LEW; and Dahl Salt-Sensitive, SS) previously found to be divergent in survival time. NBV differed by 20% ( P < 0.01; BN > SS > FHH = LEW = DA) and had a heritability (h2) of 0.56. Hence, differential survival times in our previously published study might reflect strain-dependent differences in NBV. Then studies were conducted wherein rats were catheterized and, ∼24 h later, 47% of their blood volume was removed; these rats were observed for a maximum of 4 h. In experiment 2, blood volumes were measured the day prior to hemorrhage. Percent survival and survival time did not differ among strains. To obviate possible confounding effects of blood volume determination, in experiment 3 the average NBV for each strain was used to determine hemorrhage volumes. Percent survival ( P < 0.01) and survival times ( P < 0.001) were different with DA demonstrating the best (62.5%, 190 ± 29 min) and BN the worst (0%, 52 ± 5 min) survival responses. These data indicate that both blood volume and survival time after hemorrhage in rats are heritable quantitative traits, and continue to suggest that genetic assessment of these phenotypes might lead to novel therapeutics to improve survival to hemorrhage.


2013 ◽  
Vol 45 (7) ◽  
pp. 243-255 ◽  
Author(s):  
Harold G. Klemcke ◽  
Robert M. DeKroon ◽  
Mihaela Mocanu ◽  
Jennifer B. Robinette ◽  
Oscar Alzate

We have previously identified inbred rat strains differing in survival time to a severe controlled hemorrhage (StaH). In efforts to identify cellular mechanisms and ultimately genes that are important contributors to enhanced STaH, we conducted a study to characterize potential differences in cardiac mitochondrial proteins in these rats. Inbred rats from three strains [Brown Norway/Medical College of Wisconsin (BN); Dark Agouti (DA), and Fawn Hooded Hypertensive (FHH)] with different StaH (DA = FHH > BN) were assigned to one of three treatment groups ( n = 4/strain): nonoperated controls, surgically catheterized rats, or rats surgically catheterized and hemorrhaged 24 h postsurgery. Rats were euthanized 30 min after handling or 30 min after initiation of a 26 min hemorrhage. After euthanasia, hearts were removed and mitochondria isolated. Differential protein expression was determined using 2D DIGE-based Quantitative Intact Proteomics and proteins identified by MALDI/TOF mass spectrometry. Hundreds of proteins (791) differed among inbred rat strains ( P ≤ 0.038), and of these 81 were identified. Thirty-eight were unique proteins and 43 were apparent isoforms. For DA rats (longest STaH), 36 proteins increased and 30 decreased compared with BN (shortest STaH). These 81 proteins were associated with lipid (e.g., acyl CoA dehydrogenase) and carbohydrate (e.g., fumarase) metabolism, oxidative phosphorylation (e.g., ubiquinol-cytochrome C reductase), ATP synthesis (F1ATPase), and H2S synthesis (3-mercaptopyruvate sulfurtransferase). Although we cannot make associations between these identified mitochondrial proteins and StaH, our data do provide evidence for future candidate proteins with which to consider such associations.


1969 ◽  
Author(s):  
W. B. Webb ◽  
J. K. Friedmann

2003 ◽  
Vol 196 (2) ◽  
pp. 135-141 ◽  
Author(s):  
Satoshi Ishizuka ◽  
Ayumu Takeuchi ◽  
Masahito Hagio ◽  
Mayuko Mohara ◽  
Hiroaki Sakai ◽  
...  

2020 ◽  
Vol 3 (5) ◽  
pp. 67-71
Author(s):  
Giang Trần Long

Hormone Growth (GH) và Insulin Growth Factor 1 (IGF-I) có vai trò quan trọng trong sự phát triển chiều cao cơ thể thông qua các tác động lên xương. Nhiều công trình nghiên cứu trên người và động vật cho thấy GH kích thích trực tiếp sự phát triển xương theo trục dọc bằng cách kích thích cácnguyên bào sụn trong đĩa tăng trưởng theo cơ chế nhân dòng vô tính và IGF -I kích thích các tế bào ở các giai đoạn sau bằng cách làm giảm thời gian chu kỳ tế bào. Ngoài ra, GH và IGF –I cũng phát huy tác động bổ trợ hoặc tương tác với nhau khi chúng được đưa vào cơ thể cùng nhau.


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