scholarly journals Chromosome-substituted rat strains provide insights into the genetics of placentation

2011 ◽  
Vol 43 (15) ◽  
pp. 930-941 ◽  
Author(s):  
Toshihiro Konno ◽  
Lea A. Rempel ◽  
M. A. Karim Rumi ◽  
Amanda R. Graham ◽  
Kazuo Asanoma ◽  
...  

The rat possesses a hemochorial form of placentation. Pronounced intrauterine trophoblast cell invasion and vascular remodeling characterize this type of placentation. Strain-specific patterns of placentation are evident in the rat. Some rat strains exhibit deep intrauterine trophoblast invasion and an expanded junctional zone [Holtzman Sprague-Dawley (HSD), Dahl salt sensitive (DSS)], whereas placentation sites of other rat strains are characterized by shallow invasion and a restricted junctional zone [Brown Norway (BN)]. In this report, we identified a quantitative trait that was used to distinguish strain-specific features of rat placentation. Junctional zone prolactin family 5, subfamily a, member 1 ( Prl5a1) transcript levels were significantly greater in BN rats than in HSD or DSS rats. Prl5a1 transcript levels were used as a quantitative trait to screen placentation sites from chromosome-substituted rat strains (BN chromosomes introgressed into the DSS inbred strain; DSS-BN panel). Litter size, placental weights, and fetal weights were not significantly different among the chromosome-substituted strains. Regulation of the junctional zone Prl5a1 transcript-level quantitative trait was multifactoral. Chromosome-substituted strains possessing BN chromosomes 14 or 17 introgressed into the DSS inbred rat strain displayed Prl5a1 transcript levels that were significantly different from the DSS pattern and more closely resembled the BN pattern. The in situ placental distribution of Prl5a1 mRNA and the structure of the junctional zone of DSS-BN17 rats mimicked that observed for the BN rat. Prl5a1 gene expression was also assessed in BN vs. HSD trophoblast stem cells and following reciprocal BN and HSD embryo transfer. Strain differences intrinsic to trophoblast and maternal environment were identified. In summary, we have identified chromosomes 14 and 17 as possessing regulatory information controlling a quantitative trait associated with rat placentation.

2007 ◽  
Vol 29 (1) ◽  
pp. 91-97 ◽  
Author(s):  
Justin A. Ways ◽  
Brian M. Smith ◽  
John C. Barbato ◽  
Ramona S. Ramdath ◽  
Krista M. Pettee ◽  
...  

We previously identified two inbred rat strains divergent for treadmill aerobic running capacity (ARC), the low-performing Copenhagen (COP) and the high-performing DA rats, and used an F2(COP×DA) population to identify ARC quantitative trait loci (QTLs) on rat chromosome 16 (RNO16) and the proximal portion of rat chromosome 3 (RNO3). Two congenic rat strains were bred to further investigate these ARC QTLs by introgressing RNO16 and the proximal portion of RNO3 from DA rats into the genetic background of COP rats and were named COP.DA(chr 16) and COP.DA(chr 3), respectively. COP.DA(chr 16) rats had significantly greater ARC compared with COP rats (696.7 ± 38.2 m vs. 571.9 ± 27.5 m, P = 0.03). COP.DA(chr 3) rats had increased, although not significant, ARC compared with COP rats (643.6 ± 40.9 m vs. 571.9 ± 27.5 m). COP.DA(chr 16) rats had significantly greater subcutaneous abdominal fat, as well as decreased fasting triglyceride levels, compared with COP rats ( P < 0.05), indicating that genes responsible for strain differences in fat metabolism are also located on RNO16. While this colocalization of QTLs may be coincidental, it is also possible that these differences in energy balance may be associated with the superior running performance of COP.DA(chr 16) consomic rats.


2007 ◽  
Vol 97 (04) ◽  
pp. 665-672 ◽  
Author(s):  
Hideki Ito ◽  
Hideki Hayashi ◽  
Yoshie Nagamura ◽  
Kazuyuki Toga ◽  
Yoshihisa Yamada ◽  
...  

SummaryRats are employed to investigate the role of platelets in thrombus formation under flow conditions in vivo and to evaluate the pre-clinical potential of antiplatelet drugs. While Wistar and Sprague-Dawley (SD) strains are commonly used in thrombosis models, a number of rat strains have been established. Each strain possesses genetically unique characteristics such as hypertension, hyperglycemia or hyperlipidemia. The appropriate selection of a strain might have advantages for physiological and pharmacological studies. Comparative investigation of platelet aggregation among laboratory strains of rats is useful for the development of thrombosis models. In the present study, platelet aggregation response in eight laboratory rat strains, ACI, Brown Norway (BN), Donryu, Fischer 344 (F344), LEW, SD, Wistar and WKAH, were compared. Considerable strain differences were observed in ADP-, collagen- and TRAP-induced platelet aggregation. SD and BN are high-platelet-aggregation strains, while F344 and ACI are low-response strains. In the arteriovenous shunt thrombosis model, SD formed larger thrombi than F344 andWistar rats. In the FeCl 3 -induced thrombosis model with the carotid artery, the time to occlusion of SD was significantly shorter than of F344 and ACI rats. F344 and ACI rats had significantly increased bleeding times compared with SD rat. The present study demonstrates that there are considerable strain differences in platelet aggregation among laboratory rats, which reflect thrombus formation.


Reproduction ◽  
2004 ◽  
Vol 128 (6) ◽  
pp. 857-862 ◽  
Author(s):  
Nicole R Francisco ◽  
Christen M Raymond ◽  
Paul D Heideman

Laboratory rats have been generally considered non-photoresponsive, but strains of laboratory rats have been found to be variable for this trait. Young males of both the Fischer (F344) and Brown Norway strains (BN) suppress reproductive development, food intake and body mass in short winter photoperiod (short days (SD); 8 h light:16 h darkness), and food restriction interacts with SD to enhance the effect of SD alone. Conversely, young male Harlan Sprague Dawley outbred rats, along with other outbred laboratory rats tested, have little or no response to SD except when unmasked by food restriction or other treatments, and have generally been considered nonphotoperiodic. In order to assess how widespread this trait might be among rat strains, and to test for uncoupling of reproductive and nonreproductive responses, we tested 3 additional inbred strains, including ACI, PVG and BUF rats, for photoresponsiveness and for unmasking of photoperiodic responses by food restriction. Young males of all three inbred strains exhibited photoresponsiveness in testis mass (5–20% lower in SD), seminal vesicle mass (20–50% lower in SD), and body mass (5–10% lower in SD). Food restriction also suppressed reproduction, but there was little or no interaction with the effects of photoperiod. The results are consistent with the hypothesis that laboratory rats are genetically variable for photoperiodism, and that photoresponsiveness may be widespread among inbred rat strains, as all five inbred strains tested have shown photoperiodic responses. The results are particularly important because standard research protocols may unknowingly manipulate this pathway in rats, causing unsuspected variability among or within studies.


Genetics ◽  
1982 ◽  
Vol 100 (1) ◽  
pp. 79-87
Author(s):  
Daniel W Nebert ◽  
Nancy M Jensen ◽  
Hisashi Shinozuka ◽  
Heinz W Kunz ◽  
Thomas J Gill

ABSTRACT Forty-four inbred and four randombred rat strains and 20 inbred mouse strains were examined for their Ah phenotype by determining the induction of liver microsomal aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity (EC 1.14.14.1) by intraperitoneal treatment with either β-naphthoflavone or 3-methylcholanthrene. All 48 rat strains were found to be Ah-responsive. The maximally induced hydroxylase specific activities of the ALB/Pit, MNR/Pit, MR/Pit, SHR/Pit, and Sprague-Dawley strains were of the same order of magnitude as the basal hydroxylase specific activities of the ACI/Pit, F344/Pit, OKA/Pit, and MNR/N strains. Six of the 20 mouse strains were Ah-nonresponsive (i.e. lacking the normal induction response and presumably lacking detectable amounts of the Ah receptor). The basal hydroxylase specific activities of the BDL/N, NFS/N, STAR/N, and ST/JN mouse strains were more than twice as high as the maximally induced hydroxylase specific activity of the CBA/HT strain.——To date, 24 Ah-nonresponsive mouse strains have been identified, out of a total of 68 known to have been characterized. The reasons for not finding a single Ah-nonresponsive inbred rat strain—as compared with about one Ah-nonresponsive inbred mouse strain found for every three examined—remain unknown.


2005 ◽  
Vol 98 (3) ◽  
pp. 838-844 ◽  
Author(s):  
Francis J. Golder ◽  
Andrea G. Zabka ◽  
Ryan W. Bavis ◽  
Tracy Baker-Herman ◽  
David D. Fuller ◽  
...  

Hypoxic ventilatory responses differ between rodent strains, suggesting a genetic contribution to interindividual variability. However, hypoxic ventilatory responses consist of multiple time-dependent mechanisms that can be observed in different respiratory motor outputs. We hypothesized that strain differences would exist in discrete time-dependent mechanisms of the hypoxic response and, furthermore, that there may be differences between hypoglossal and phrenic nerve responses to hypoxia. Hypoglossal and phrenic nerve responses were assessed during and after a 5-min hypoxic episode in anesthetized, vagotomized, and ventilated rats from four inbred strains: Brown Norway (BN), Fischer 344 (FS), Lewis (LW), and Piebald-viral-Glaxo (PVG). During baseline, burst frequency was higher in PVG than LW rats ( P < 0.05), phrenic burst amplitude was higher in PVG vs. other strains ( P < 0.05), and hypoglossal burst amplitude was higher in PVG and BN vs. FS and LW ( P < 0.05). During hypoxia, burst frequency did not change in BN or LW rats, but it increased in PVG and FS rats. The phrenic amplitude response was smallest in PVG vs. other strains ( P < 0.05), and the hypoglossal response was similar among strains. Short-term potentiation posthypoxia was slowest in FS and fastest in LW rats ( P < 0.05). Posthypoxia frequency decline was absent in PVG, but it was observed in all other strains. Augmented breaths were observed during hypoxia in FS rats only. Thus genetic differences exist in the time domains of the hypoxic response, and these are differentially expressed in hypoglossal and phrenic nerves. Furthermore, genetic diversity observed in hypoxic ventilatory responses in unanesthetized rats may arise from multiple neural mechanisms.


1992 ◽  
Vol 73 (4) ◽  
pp. 1608-1613 ◽  
Author(s):  
L. J. Xu ◽  
S. Sapienza ◽  
T. Du ◽  
S. Waserman ◽  
J. G. Martin

The purpose of the study was to investigate the relationships between upper airways responses and pulmonary responses of two strains of highly inbred rats to inhaled antigen. To do this we measured the upper and lower airways resistance for 60 min after challenge of Brown-Norway rats (BN; n = 13) and an inbred rat strain (MF; n = 11), derived from Sprague-Dawley, with aerosolized ovalbumin (OA). Rats were actively sensitized with OA (1 mg sc) using Bordetella pertussis as an adjuvant. Two weeks later the animals were anesthetized and challenged. Tracheal pressure, esophageal pressure, and airflow were measured, from which total pulmonary resistance was partitioned into upper airway and lower pulmonary resistance (RL). The peak upper airway response to inhaled OA was similar in BN (1.89 +/- 0.66 cmH2O.ml-1.s; n = 7) and MF (2.85 +/- 0.68 cmH2O.ml-1.s; n = 6). The lower airway response to OA challenge was substantially greater in BN, and RL changed from 0.07 +/- 0.01 to 0.34 +/- 0.13 (n = 6; P < 0.05). The MF did not have any significant increase in RL after challenge; the baseline RL was 0.12 +/- 0.02 and only reached a peak value of 0.15 +/- 0.05 (n = 5; P = NS). Lower airway responsiveness of BN (n = 10) to serotonin, an important mediator early allergic airway responses, was similar to MF (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)


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.


2002 ◽  
Vol 93 (3) ◽  
pp. 974-983 ◽  
Author(s):  
Matthew R. Hodges ◽  
Hubert V. Forster ◽  
Paula E. Papanek ◽  
Melinda R. Dwinell ◽  
Genevieve E. Hogan

Our purpose in this study was to identify different ventilatory phenotypes among four different strains of rats. We examined 114 rats from three in-house, inbred strains and one outbred strain: Brown Norway (BN; n = 26), Dahl salt-sensitive ( n = 24), Fawn-hooded Hypertensive (FHH: n = 27), and outbred Sprague-Dawley rats (SD; n = 37). We measured eupneic (room air) breathing and the ventilatory responses to hypoxia (12% O2-88% N2), hypercapnia (7% CO2), and two levels of submaximal exercise. Primary strain differences were between BN and the other strains. BN rats had a relatively attenuated ventilatory response to CO2 ( P < 0.001), an accentuated ventilatory response to exercise ( P < 0.05), and an accentuated ventilatory roll-off during hypoxia ( P < 0.05). Ventilation during hypoxia was lower than other strains, but hyperventilation during hypoxia was equal to the other strains ( P > 0.05), indicating that the metabolic rate during hypoxia decreased more in BN rats than in other strains. Another strain difference was in the frequency and timing components of augmented breaths, where FHH rats frequently differed from the other strains, and the BN rats had the longest expiratory time of the augmented breaths (probably secondary to the blunted CO2 sensitivity). These strain differences not only provide insight into physiological mechanisms but also indicate traits (such as CO2 sensitivity) that are genetically regulated. Finally, the data establish a foundation for physiological genomic studies aimed at elucidating the genetics of these ventilatory control mechanisms.


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.


2006 ◽  
Vol 101 (4) ◽  
pp. 1097-1103 ◽  
Author(s):  
S. E. Davis ◽  
G. Solhied ◽  
M. Castillo ◽  
M. Dwinell ◽  
D. Brozoski ◽  
...  

Ventilatory sensitivity to CO2 in awake adult Brown Norway (BN) rats is 50–75% lower than in adult Sprague-Dawley (SD) and salt-sensitive Dahl S (SS) rats. The purpose of the present study was to test the hypothesis that this difference would be apparent during the development of CO2 sensitivity. Four litters of each strain were divided into four groups such that rats were exposed to 7% inspired CO2 for 5 min in a plethysmograph every third day from postnatal day (P) 0 to P21 and again on P29 and P30. From P0 to P14, CO2 exposure increased pulmonary ventilation (V̇e) by 25–50% in the BN and SD strains and between 25 to over 200% in the SS strain. In all strains beginning around P15, the response to CO2 increased progressively reaching a peak at P19–21 when V̇e during hypercapnia was 175–225% above eucapnia. There were minimal changes in CO2 sensitivity between P21 and P30, and at both ages there were minimal between-strain differences. At P30, the response to CO2 in the SS and SD strains was near the adult response, but the response in the BN rats was 100% greater at P30 than in adults. We conclude that 1) CO2-sensing mechanisms, and/or mechanisms downstream from the chemoreceptors, change dramatically at the age in rats when other physiological systems are also maturing (∼P15), and 2) there is a high degree of age-dependent plasticity in CO2 sensitivity in rats, which differs between strains.


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