1. Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes of male Otsuka Long Evans Tokushima Fatty (OLETF) rats. 2. Our congenic lines, produced by transferring Dmo1 chromosomal segments from the non-diabetic Brown Norway (BN) rat into the OLETF strain, have confirmed the strong, wide-range therapeutic effects of Dmo1 on dyslipidaemia, obesity and diabetes in the fourth (BC4) and fifth (BC5) generations of congenic animals. Analysis of a relatively small number of BC5 rats (n = 71) suggested that the critical Dmo1 interval lies within a
Insulin resistance is associated with hypertension by mechanisms likely involving the kidney. To determine how the major apical sodium transporter of the thick ascending limb, the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) is regulated by high-fat feeding, we treated young male, Fischer 344 X Brown Norway (F344BN) rats for 8 wk with diets containing either normal (NF, 4%) or high (HF, 36%) fat, by weight, primarily as lard. HF-fed rats had impaired glucose tolerance, increased urine excretion of 8-isoprostane (a marker of oxidative stress), increased protein levels for NKCC2 (50-125%) and the renal outer medullary potassium channel (106%), as well as increased natriuretic response to furosemide (20-40%). To test the role of oxidative stress in this response, in study 2, rats were fed the NF or HF diet plus plain drinking water, or water containing N(G)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor (100 mg/l), or tempol, a superoxide dismutase mimetic (1 mmol/l). The combination of tempol with HF nullified the increase in medullary NKCC2, while l-NAME with HF led to the highest expression of medullary NKCC2 (to 498% of NF mean). However, neither of these drugs dramatically affected the elevated natriuretic response to furosemide with HF. Finally, l-NAME led to a marked increase in blood pressure (measured by radiotelemetry), which was significantly enhanced with HF. Mean arterial blood pressure at 7 wk was as follows (mmHg): NF, 100 +/- 2; NF plus l-NAME, 122 +/- 3; and HF plus l-NAME, 131 +/- 2. Overall, HF feeding increased the abundance of NKCC2. Inappropriately high sodium reabsorption in the thick ascending limb via NKCC2 may contribute to hypertension with insulin resistance.
Future adaptation to changes in the environment depends on the existence of additive genetic variances within populations. Recently, considerable attention has also been given to the non-additive component, which plays an important role in inbreeding depression and bottleneck situations. In this study, I used data from a North Carolina II crossing experiment, analysed with restricted maximum-likelihood methods, to estimate the additive and dominance genetic (co)variances for eight quantitative characters in two different-sized populations of Scabiosa canescens, a rare and threatened plant in Sweden. There was no evidence for genetic erosion in the small Hällestad population ( approximately 25 individuals) relative to the large Ahus population ( approximately 5000 individuals). In fact, slightly higher heritabilities were found in the Hällestad population. The additive genetic variance was statistically significant for all traits in both populations, but only a few additive covariances reached significance. The Hällestad population also had higher mean levels and more traits with significant dominance variance than the Ahus population. The variance attributable to maternal effects was too low to be considered significant. There was only a weak correspondence between heritabilities for each trait in the present study and previous estimates based on open-pollinated families of the same populations, but the mean heritability (over characters) was consistent between the studies.
The effects of aging on cardiovascular function and cardiac structure were determined in a rat model recommended for gerontological studies. A cross-sectional analysis assessed cardiac changes in male Fischer 344 x Brown Norway F1 hybrid rats (FBN) from adulthood to the very aged (n = 6 per 12-, 18-, 21-, 24-, 27-, 30-, 33-, 36-, and 39-mo-old group). Rats underwent echocardiographic and hemodynamic analyses to determine standard values for left ventricular (LV) mass, LV wall thickness, LV chamber diameter, heart rate, LV fractional shortening, mitral inflow velocity, LV relaxation time, and aortic/LV pressures. Histological analyses were used to assess LV fibrotic infiltration and cardiomyocyte volume density over time. Aged rats had an increased LV mass-to-body weight ratio and deteriorated systolic function. LV systolic pressure declined with age. Histological analysis demonstrated a gradual increase in fibrosis and a decrease in cardiomyocyte volume density with age. We conclude that, although significant physiological and morphological changes occurred in heart function and structure between 12 and 39 mo of age, these changes did not likely contribute to mortality. We report reference values for cardiac function and structure in adult FBN male rats through very old age at 3-mo intervals.
Expression of mRNA for interleukin-6, interleukin-6Delta3, and interleukin-6Delta5 was detected in placental tissue (second and third trimesters of pregnancy) and spleen of mice immunized with sheep erythrocytes in high dose. We hypothesize that translation of mRNA yields proteins capable of binding to individual subunits of the interleukin-6 receptor and possessing effector functions.
Purified murine tubular basement membrane (TBM) antigen (molecular weight, 32,000) induced interstitial lesions in Brown Norway (BN) rats. TBM antigen prepared from mice of 3 inbred strains--BALB/c, C3H/He, and C57BL/6--and outbred ddY mice possessed both antigenicity and nephritogenecity. Using these TBM antigens, the roles of humoral and cellular immunity in the development of interstitial nephritis (IN) and the genetic control of the induction of IN in inbred mice were investigated. BALB/c mice were highly susceptible to IN and showed a high antibody response and a high lymphocyte proliferative response to syngeneic and allogeneic TBM antigen, whereas C57BL/6 mice did not. C3H/He mice, in which minimal interstitial lesions developed, showed a high antibody response but a low proliferative response of T cells to TBM antigen. TBM antigen sensitized T cells induced interstitial lesions, but anti-TBM antisera did not do so. Thus, the development of IN seemed to be related closely to cellular immunity. Further studies with their hybrids, backcrosses, congenic mice, and recombinant mice suggested that the induction of IN and the immune response to TBM antigen are controlled by 1 or a few dominant genes, whose loci are within, or closely linked to, the H-2 complex.
This study shows how a Gibbs sampling approach can be used for Bayesian inference of inbreeding depression. The method presented is mainly concerned with organisms that can be both selfed and outcrossed. Tests performed on simulated data with unequal variances and missing observations show that the method works well. Real data from the plant Scabiosa canescens is also analyzed.
Evidence exists that mitochondrial content and/or function is reduced in muscle of aging individuals. The purposes of this study were to investigate the contribution of outer membrane protein import and assembly processes to this decline and to determine whether the assembly process could adapt to chronic contractile activity (CCA). Tom40 assembly into the translocases of the outer membrane (TOM complex) was measured in subsarcolemmal mitochondria obtained from young (6 mo old) and aged (36 mo old) Fischer 344 x Brown Norway animals. While the initial import of Tom40 did not differ between young and aged animals, its subsequent assembly into the final approximately 380 kDa complex was 2.2-fold higher (P
RefSource: Am J Physiol Cell Physiol. 2010 Jun;298(6):C1298-300
Quantitative Trait Locus (QTL) analysis was used to identify the loci of polygenic characteristics in a study of the genetic determination of the behavior of rats with inherited stress-induced arterial hypertension (ISIAH rats). Analysis was performed using males of two populations of F2 hybrids (ISIAH x WAG) of different ages: 3-4 (n = 106) and six months (n = 130). Chromosomes 2 and 16 in the young population of F2 rats showed significant associations between two characteristics of behavior in ISIAH rats and genetic loci: a) the rats' motor activity at the periphery of the open field area with loci in the regions of markers D2Rat157-D2Rat88 (LOD score 4.83; p = 0.000058) and D16Rat32 (LOD score 3.71; p = 0.00023). Together, these two loci accounted for 42.9% of the trait variability; b) the rats' motor activity during the first minute of the open field test and loci in the region of the marker D16Rat58 (LOD score 3.78; p = 0.00028). Results obtained by QTL analysis demonstrated a relationship between the genetic control of these traits and the animals' age.