Interacting quantitative trait loci control phenotypic variation in murine estradiol-regulated responses

The steroid hormone estradiol (E2) elicits a spectrum of systemic and uterotropic responses in vivo. For example, E2 treatment of ovariectomized adult and sexually immature rodents leads to uterine leukocytic infiltration, cell proliferation, and organ growth. E2-regulated growth is also associated with a variety of normal and pathological phenotypes. Historically, the uterine growth response has been used as the key model to understand the molecular and biochemical mechanisms underlying E2-dependent growth. In this study, genome exclusion mapping identified two quantitative trait loci (QTL) in the mouse, Est2 and Est3 on chromosomes 5 and 11, respectively, that control the phenotypic variation in uterine wet weight. Both QTL are linked to a variety of E2-regulated genes, suggesting that they may represent loci within conserved gene complexes that play fundamental roles in mediating the effects of E2. Interaction and multiple trait analyses using the uterine leukocyte response and wet weight suggest that Est4, a QTL on chromosome 10, may encode an interacting factor that influences the quantitative variation in both responses. Our results show that E2-dependent responses can be genetically controlled and that a genetic basis may underlie the variation observed in many E2-dependent phenotypes.     

B7-1 and B7-2 monoclonal antibodies modulate the severity of murine Lyme arthritis

We assessed the role of B7-1 and B7-2 costimulatory molecules on the course of murine Lyme borreliosis because experimental Lyme arthritis is dependent, at least partially, upon the development of the host immune response and these costimulatory molecules have been implicated in CD4+ T-cell differentiation. We demonstrated that Borrelia burgdorferi infection upregulated the surface expression of B7-1 and B7-2 in macrophages and B7-2 expression in B cells. Anti-B7-2 monoclonal antibody (MAb) or both anti-B7-2 and anti-B7-1 MAbs produced a dose-dependent increase in the severity of Lyme arthritis in C3H/HeN mice. In contrast, the administration of an anti-B7-1 MAb reduced the degree of arthritis. These effects occurred independently of significant alteration in B. burgdorferi-specific immune responses, including splenocyte proliferative responses to B. burgdorferi, B. burgdorferi antibody levels and specificity, and mRNA levels of gamma interferon, interleukin-4 (IL-4), IL-10, and IL-12 in the spleen. These results demonstrate that signaling delivered by B7-1 and B7-2 plays a role in determining the severity of acute murine Lyme arthritis.     

Mapping quantitative trait loci for immune capacity in the pig

Immune capacity traits show considerable genetic variation in outbred populations. To identify quantitative trait loci (QTLs) for immune capacity in the pig, various measures of immune function (total and differential leukocyte counts, neutrophil phagocytosis, mitogen-induced proliferation, IL-2 production, and virus induced IFN-alpha production in whole blood cultures, and Ab responses to two Escherichia coli antigens) were determined in 200 F2 animals from a wild pig-Swedish Yorkshire intercross. The pedigree has been typed for 236 genetic markers covering all autosomes, the X chromosome and the X/Y pseudoautosomal region. Through interval mapping using a least-squares method, four QTLs with significant effects were identified; one for total leukocyte counts, one for mitogen-induced proliferation, one for prevaccination levels of Abs to E. coli Ag K88, and one for Ab response to the O149 Ag. In addition, several putative QTLs were indicated. The results from the present study conclusively show that it is possible to identify QTLs for immune capacity traits in outbred pig populations by genome analysis.     

Least squares interval mapping of quantitative trait loci under the infinitesimal genetic model in outbred populations

Genetic marker and phenotypic data for a quantitative trait were simulated on 20 paternal half-sib families with 100 progeny to investigate properties of within-family-regression interval mapping of a postulated single quantitative trait locus (QTL) in a marker interval under the infinitesimal genetic model, which has been the basis of the application of quantitative genetics to genetic improvement programs, and to investigate use of the infinitesimal model as null hypothesis in testing for presence of a major QTL. Genetic effects on the marked chromosome were generated based on a major gene model, which simulated a central biallelic QTL, or based on 101 biallelic QTL of equal effect, which approximated the infinitesimal model. The marked chromosome contained 0, 3.3%, 13.3%, or 33.3% of genetic variance and heritability was 0.25 or 0.70. Under the polygenic model with 3.3% of genetic variance on the marked chromosome, which corresponds to the infinitesimal model for the bovine, significant QTL effects were found for individual families. Correlations between estimates of QTL effects and true chromosome substitution effects were 0.29 and 0.47 for heritabilities of 0.25 and 0.70 but up to 0.85 with 33.3% of polygenic variance on the marked chromosome. These results illustrate the potential of marker-assisted selection even under the infinitesimal genetic model. Power of tests for presence of QTL was substantially reduced when the polygenic model with 3.3% of genetic variance on the chromosome was used as a null hypothesis. The ability to determine whether genetic variance on a chromosome was contributed by a single QTL of major effect or a large number of QTL with minor effects, corresponding to the infinitesimal model, was limited.     

Identification of quantitative trait loci influencing wood specific gravity in an outbred pedigree of loblolly pine

We report the identification of quantitative trait loci (QTL) influencing wood specific gravity (WSG) in an outbred pedigree of loblolly pine (Pinus taeda L.). QTL mapping in an outcrossing species is complicated by the presence of multiple alleles (> 2) at QTL and marker loci. Multiple alleles at QTL allow the examination of interaction among alleles at QTL (deviation from additive gene action). Restriction fragment length polymorphism (RFLP) marker genotypes and wood specific gravity phenotypes were determined for 177 progeny. Two RFLP linkage maps were constructed, representing maternal and paternal parent gamete segregations as inferred from diploid progeny RFLP genotypes. RFLP loci segregating for multiple alleles were vital for aligning the two maps. Each RFLP locus was assayed for cosegregation with WSG QTL using analysis of variance (ANOVA). Five regions of the genome contained one or more RFLP loci showing differences in mean WSG at or below the P = 0.05 level for progeny as grouped by RFLP genotype. One region contained a marker locus (S6a) whose QTL-associated effects were highly significant (P > 0.0002). Marker S6a segregated for multiple alleles, a prerequisite for determining the number of alleles segregating at the linked QTL and analyzing the interactions among QTL alleles. The QTL associated with marker S6a appeared to be segregating for multiple alleles which interacted with each other and with environments. No evidence for digenic epistasis was found among the five QTL.     

Quantitative trait loci that modify the severity of spotting in piebald mice

OBJECTIVE: to evaluate the diagnostic and therapeutic role of emergency hemodynamic studies, in the coronary intensive care (UCI). STUDY DESIGN: Retrospective study of--patients (P) submitted to emergency catheterization. PATIENTS: 183 P (152 M and 31 F), mean age 56 +/- 11.5 years, admitted to UCI of Hospital Santa Marta and who had cardiac catheterization performed, between October 88 and November 92. METHODS: Patient clinical files were reviewed. We considered the reasons for emergency cardiac catheterization; final diagnosis; complications in the first 24 hours; catheterization role in the therapeutic orientation. RESULTS: Reasons for hemodynamic study were: coronary artery disease (CAD) in 127 P (69%); aortic dissection in 33 P (18%); valvular disease in 19 P (10%) and other in 4 P (3%). Clinical diagnosis was confirmed in 92% and changed in 8% by hemodynamic study results. Left main coronary artery disease was diagnosed in 6.5% of CAD patients. Coronary artery disease was excluded in 5 P with previous CAD diagnosis, in 19 P with aortic dissection and in 11 valvular patients. 32% of P were sent to emergent surgery: 93% ascending aortic dissection and 20% of CAD, 76% of valvular disease. The hemodynamic study was decisive in the therapeutic option of myocardial revascularization in 77% of P with CAD: 39 emergent PTCA (31%), 13 primary (33%) and 14 P oriented to elective PTCA (11%); 26 emergent surgery and 19 P oriented to elective surgery (15%). The emergency cardiac catheterization mortality rate was 0.5%, and the morbidity 2.7%. CONCLUSIONS: The contribution of Hemodynamic Department to UCI was decisive in the diagnostic and therapeutic orientation of critical patients.     

Identification of quantitative trait loci involved in contextual and auditory-cued fear conditioning in BXD recombinant inbred strains.

Fear conditioning shows associations formed between contextual or auditory stimuli with an unconditioned stimulus. Inbred mouse strains differ in their ability to demonstrate fear conditioning, suggesting at least a partial genetic influence. The present study identified the possible chromosomal loci regulating fear conditioning in BXD recombinant inbred strains using quantitative trait loci (QTL) analysis. Estimates of heritability for all 3 measures of conditioning were about .28. Correlational analyses between genetic markers and strain means identified multiple putative QTLs. The strongest associations were on Chromosomes 1 and 17 for freezing to the context, Chromosome 12 for freezing to an altered context, and Chromosome 1 for freezing to the auditory stimulus. Overlapping QTLs may indicate some common genes that underlie aspects of this learning task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estimation of effects of quantitative trait loci in large complex pedigrees

A method was derived to estimate effects of quantitative trait loci (QTL) using incomplete genotype information in large outbreeding populations with complex pedigrees. The method accounts for background genes by estimating polygenic effects. The basic equations used are very similar to the usual linear mixed model equations for polygenic models, and segregation analysis was used to estimate the probabilities of the QTL genotypes for each animal. Method R was used to estimate the polygenic heritability simultaneously with the QTL effects. Also, initial allele frequencies were estimated. The method was tested in a simulated data set of 10,000 animals evenly distributed over 10 generations, where 0, 400 or 10,000 animals were genotyped for a candidate gene. In the absence of selection, the bias of the QTL estimates was < 2%. Selection biased the estimate of the Aa genotype slightly, when zero animals were genotyped. Estimates of the polygenic heritability were 0.251 and 0.257, in absence and presence of selection, respectively, while the simulated value was 0.25. Although not tested in this study, marker information could be accommodated by adjusting the transmission probabilities of the genotypes from parent to offspring according to the marker information. This renders a QTL mapping study in large multi-generation pedigrees possible.     

Selective anti-inflammatory action of interleukin-11 in murine Lyme disease: arthritis decreases while carditis persists

The role of interleukin (IL)-11, a cytokine with potent anti-inflammatory properties, in murine Lyme disease was investigated. Borrelia burgdorferi-infected mice treated with IL-11 developed less arthritis than did control animals. In contrast, IL-11 blocking antibodies increased Lyme arthritis. Murine Lyme carditis was not affected by either IL-11 or IL-11 antibodies. Administration of IL-11 was associated with increased production of mRNA for IL-12 and inducible nitric oxide synthase but not interferon-gamma or IL-4 in B. burgdorferi-infected mice, suggesting a predominant effect of IL-11 on the innate immune response. These data show that IL-11 selectively reduced joint but not cardiac inflammation caused by B. burgdorferi in mice.     

CD8+ T cells are activated during the early Th1 and Th2 immune responses in a murine Lyme disease model

T-helper responses following Borrelia burgdorferi infection in mice determine susceptibility to Lyme arthritis. The ratio of interleukin 4-positive, CD4+ to gamma interferon (IFN-gamma)-positive, CD4+ T cells was significantly greater in infected BALB/cJ mice than in infected C3H/HeJ mice. Increased numbers of IFN-gamma-producing cells predicted greater arthritis severity, and CD8+ T cells were the main source of IFN-gamma in both strains.     

Identification of quantitative trait loci affecting carcass composition in swine: II. Muscling and wholesale product yield traits

A genomic scan was conducted on 540 reciprocal backcross Meishan x White composite pigs for hot carcass weight (HCWT); loin eye area (LOIN); carcass length (CRCL); belly weight (BELLY); and weight of trimmed ham, loin, picnic, and Boston butt adjusted to a constant live (TWPLWT) or carcass (TWPCWT) weight. Genetic markers spanned the entire porcine linkage map and were spaced at approximately 20-cM intervals. Grandparental breed of origin for all chromosomal segments was determined using multipoint linkage procedures, and a least squares regression analysis was conducted. Nominal P-values were converted to a genome-wide level of significance to adjust for the number of tests actually conducted. Seven associations were significant at the genome-wide level relating to chromosomes 1 (SSC 1), 7 (SSC 7), and X (SSC X). The SSC 1 region affected LOIN, TWPLWT, and TWPCWT; SSC 7 affected HWCT and CRCL; and SSC X affected TWPLWT and TWPCWT. Twelve associations relating to seven chromosomal regions (including SSC 1 and X) presented suggestive evidence for quantitative trait loci (QTL), and many of these regions are likely to contain QTL. Chromosomes 8 and 14 had two and three traits with suggestive evidence for QTL, respectively. Many pleiotropic effects were detected for regions on SSC 1, 7, 14, and X in this study and a companion study looking for fat deposition QTL in the same population. In addition, SSC 4 was nearly significant for CRCL in the same region identified as affecting backfat in a wild boar x Large White population. These results expand our knowledge of the inheritance of quantitative traits and are directly relevant to composite populations containing Meishan germplasm.     

Confirmation of quantitative trait loci for ethanol sensitivity in long-sleep and short-sleep mice

PURPOSE: To determine the efficacy of the combination of cisplatin, fluorouracil, and high-dose l-leucovorin (PFL) as organ-preserving induction therapy followed by radiotherapy in untreated patients with advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: This was a phase II study of PFL in 47 patients with resectable stage III (n = 20) and IV (n = 27) M0 squamous cell carcinoma of the head and neck, including larynx (n = 20), hypopharynx (n = 14), and oropharynx (n = 13). The PFL regimen consisted of cisplatin 25 mg/m2 on days 1 through 5, fluorouracil 800 mg/m2 CI on days 2 through 6, and l-leucovorin 250 mg/m2 on days 1 through 6, all by continuous intravenous infusion every 21 to 28 days for three courses. The primary study endpoint was initial response to and local disease control rate with PFL as induction chemotherapy, with an aim to confirm the previously reported complete response rate of 60% to 70%. RESULTS: Of 47 patients enrolled, 46 were evaluable for response to PFL, 14 (30%) achieved a complete response, and 25 (54%) achieved a partial response, for an overall response rate of 84%. Of 39 patients evaluable for response after radiation therapy, 27 (69%) achieved a complete response and 11 (28%) a partial response. Local disease control was achieved in 37 of 46 (80%). Grade 3 or 4 toxic effects occurred frequently, with neutropenia in 27 (59%) of 46 evaluable patients, thrombocytopenia in 30%, mucositis in 41%, diarrhea in 13%, and nausea/ vomiting in 13%, but there were no treatment-related deaths. With a median follow-up of 35 months there have been nine recurrences (four local/regional and five distant) and 17 deaths (12 in patients with disease progression and five not directly related to the primary tumor). Second primary tumors have developed in six patients. At 3 years 62% of the patients remain alive with no disease progression, and the 3-year survival estimate with preserved organ function is 66%. CONCLUSION: PFL induction chemotherapy produced only a modest complete response rate, possibly due to suboptimal dose intensity, and was associated with substantial, although not life-threatening, toxicity. Newer regimens and treatment modalities are still needed in the management of advanced squamous cell carcinoma of the head and neck.     

Detection of quantitative trait loci in outbred populations with incomplete marker data

AcrA protein is a component of the multi-drug efflux complex AcrAB-TolC of Escherichia coli. Judged by the hypersusceptibility phenotype of acrA mutants, the AcrAB-TolC system pumps out an extraordinarily wide variety of antibiotics, chemotherapeutic agents, detergents and dyes. This complex traverses both the inner and outer membranes of E. coli and catalyzes efflux of the drugs directly into the medium. The coordinated operation of the inner membrane transporter AcrB and outer membrane channel TolC is thought to be mediated by AcrA. The latter is a lipoprotein located in the periplasmic space. We show here that a lipid-deficient derivative of AcrA is functionally active as demonstrated by the complementation of the hypersusceptibility phenotype of the acrA mutant. Purified non-lipidated and intact forms of AcrA were able to restore, with similar efficiency, the activity of AcrA-dependent efflux of erythromycin in Ca2+-sucrose-treated E. coli cells. Using analytical ultracentrifugation and dynamic light scattering techniques we determined hydrodynamic properties of the non-lipidated AcrA and found that AcrA exists in solution as a highly asymmetric monomeric molecule with an axial ratio of 8. This elongated shape of AcrA is compatible with the hypothesis that this protein spans the periplasmic space coordinating the concerted operation of inner and outer membrane components of the complex.     

Identification of the gene loci that predispose to rheumatoid arthritis

We have searched the human genome for genes that predispose to rheumatoid arthritis (RA) using fluorescence-based microsatellite marker analysis and affected sib-pair linkage study. A panel of 41 Japanese families, each with at least two affected siblings, was typed for genome-wide 358 polymorphic microsatellite marker loci. Markers were amplified by the PCR using fluorescence-tagged primers and sized based on the difference of CA repeats on DNA. Linkage analysis was made using maximum lod score (MLS). The MLS for D1S214 and D8S556 was 3.27 and 3.33, while the MLS for the HLA-DRB1 region was <3.0. According to detailed analysis by single-point analysis using MAPMAKER/SIBS, the MLS for D1S253 and D1S214 was 3.77 and 3.58. The MLS by multipoint analysis was 6.13 for D1S253. The MLS for D8S556 by single-point analysis was 4.20. The MLS for DXS1232 was 2.35 by single-point analysis, whereas the MLS for the region 2 cM right to DXS1232 and the region between DXS1227 and DXS1200 was 3.03 and 2.93 by multi-point analysis. Three principal chromosome regions of linkage, D1S253/214, D8S556 and DXS1232, have been identified which we call RA1, RA2 and RA3 for RA disease loci.     

Genetic immunization generates cellular and humoral immune responses against the nonstructural proteins of the hepatitis C virus in a murine model

Exposure to hepatitis C virus (HCV) is associated with a high prevalence of persistent viral infection and the development of chronic liver disease and hepatocellular carcinoma. Recovery from acute infection may depend upon the generation of broad-based cellular immune responses to viral structural and nonstructural proteins. We used the DNA-based immunization approach in BALB/c mice to determine whether the HCV nonstructural proteins NS3, NS4, and NS5 will induce Ab responses, CD4+ Th cell proliferation, and cytokine release in response to stimulation by recombinant proteins as well as generate CD8+ CTL activity both in vitro and in vivo. We found that the nonstructural proteins were particularly good immunogens and produced cellular immune responses when administered as a DNA construct. Indeed, a tumor model was established following inoculation of syngenic SP2/0 cells stably transfected with NS5. We observed protection against tumor formation and growth only in mice immunized with the NS5-encoding DNA construct, establishing the generation of significant CTL activity in vivo by this technique. The results indicate that genetic immunization may define the cellular immune response of the host to HCV nonstructural proteins and is a promising approach for vaccine development.     

Effects of immunopharmacological compounds in the Lyme arthritis model using normal and SCID mice

The murine Lyme borreliosis causes a special type of arthritis whose development appears to be controlled by a functioning immune system. Immunocompetent C3H and severe combined immunodeficient (SCID) mice were infected with Borrelia burgdorferi (strain SH-2-82) to induce experimental Lyme disease. Expression of clinical symptoms was mild to very moderate in the C3H but more rapidly developing and severe in the SCID mouse. Various pharmacological compounds, such as anti-inflammatory and immunosuppressive drugs, monoclonal antibodies and other miscellaneous agents, were investigated for profiling their effects in this model in both mouse strains. Several disease parameters were assessed, in particular paw swelling. The use of these various compounds provided further evidence that experimental borreliosis in mice represents a special type of arthritis which has no autoimmune basis and which requires productive infection with Borrelia burgdorferi. In addition, when comparing these results with those obtained in other mainly immune driven arthritis models commonly used in inflammation research, it is concluded that this arthritis model is not suitable for the therapeutic assessment of antiinflammatory agents.     

Quantitative trait loci disposing for both experimental arthritis and encephalomyelitis in the DA rat; impact on severity of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis and antibody isotype pattern

Quantitative trait loci (QTL) controlling inflammatory diseases with different organ specificity may hypothetically either be unique for one disease or shared among different diseases. We have investigated whether five non-MHC QTL controlling susceptibility to experimental arthritis in the DA rat also influence myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in an F2 intercross between inbred DA and PVG.RT1a rats. Two of the five chromosome regions affecting arthritis in the DA rat also regulate phenotypes of EAE. The DA allele at markers in Cia3 (collagen-induced arthritis QTL) on chromosome 4 is associated with more severe EAE and high levels of anti-MOG antibodies of the IgG2c subclass. Since production of antibodies of the IgG2c subclass may be stimulated by Th1 cells, and there is previous evidence that such cells promote EAE, it is possible that both of the studied phenotypes are controlled by the same gene or genes regulating Th1/Th2 cell differentiation. Furthermore, we show that Oia2 (oil-induced arthritis QTL) on chromosome 4 regulates levels of anti-MOG antibodies of the IgG1 subclass and of anti-MOG IgE, but that this gene region does not affect clinical disease severity in our study. Since production of IgE and IgG1 may be stimulated by Th2 cells, this QTL may also control Th1/Th2 bias. We conclude that Cia3 and Oia2 regulate MOG-induced EAE in rats. Furthermore, since both EAE and arthritis phenotypes co-localize to these gene regions, they may harbor genes which are key regulators of pathogenic immune responses.     

Polygenic mutation in Drosophila melanogaster: genetic interactions between selection lines and candidate quantitative trait loci

We have investigated genetic interactions between spontaneous mutations affecting abdominal and sternopleural bristle number that have accumulated in 12 long-term selection lines derived from an inbred strain, and mutations at 14 candidate bristle number quantitative trait loci. The quantitative test for complementation was to cross the selection lines to an inbred wild-type strain (the control cross) and to a derivative of the control strain into which the mutant allele at the candidate locus to be tested was substituted (the tester strain). Genetic interactions between spontaneous mutations affecting bristle number and the candidate locus mutations were common, and in several cases the interaction effects were different in males and females. Analyses of variance of the (tester- control) differences among and within groups of replicate lines selected in the same direction for the same trait showed significant group effects for several candidate loci. Genetically, the interactions could be caused by allelism of, and/ or epistasis between, spontaneous mutations in the selection lines and the candidate locus mutations. It is possible that much of the response to selection was from new mutations at candidate bristle number quantitative trait loci, and that for some of these loci, mutation rates were high.     

Mapping quantitative trait loci with dominant and missing markers in various crosses from two inbred lines

Bacterial resistance to beta-lactam antibiotics, a clinically worrying and recurrent problem, is often due to the production of beta-lactamases, enzymes that efficiently hydrolyze the amide bond of the beta-lactam nucleus. Imipenem and other carbapenems escape the activity of most active site serine beta-lactamases and have therefore become very popular drugs for antibacterial chemotherapy in the hospital environment. Their usefulness is, however, threatened by the appearance of new beta-lactamases that efficiently hydrolyze them. This study is focused on the structure and properties of two recently described class A carbapenemases, produced by Serratia marcescens and Enterobacter cloacae strains and leads to a better understanding of the specificity of beta-lactamases. In turn, this will contribute to the design of better antibacterial drugs. Three-dimensional models of the two class A carbapenemases were constructed by homology modeling. They suggested the presence, near the active site of the enzymes, of a disulfide bridge (C69-C238) whose existence was experimentally confirmed. Kinetic parameters were measured with the purified Sme-1 carbapenemase, and an attempt was made to explain its specific substrate profile by analyzing the structures of minimized Henri-Michaelis complexes and comparing them to those obtained for the "classical" TEM-1 beta-lactamase. The peculiar substrate profile of the carbapenemases appears to be strongly correlated with the presence of the disulfide bridge between C69 and C238.     

Genetic mapping of two new blood pressure quantitative trait loci in the rat by genotyping endothelin system genes

The endothelin system, consisting of a series of potent vasoconstrictor peptides and their receptors, is potentially important in the control of blood pressure. We found that the gene coding for endothelin-2 (ET2), also known as vasoctive intestine peptide, cosegregated strongly with systolic blood pressure in a F2 population [F2(S x LEW)] derived from a cross of the Dahl salt-sensitive (S) rat and the Lewis (LEW/NCrlBR) (LEW) rat. The ET2 locus was assigned to rat chromosome 5. The testis-specific histone (HITH) locus also strongly cosegregated with blood pressure in the F2(S x LEW) population and was assigned to rat chromosome 17. Genetic maps of the regions containing the quantitative trait loci (QTL) for blood pressure on chromosomes 5 and 17 were constructed and the QTL were localized using the MAPMAKER/QTL program. The rat genes for endothelin-1, endothelin-3, and endothelin receptor A did not cosegregate with blood pressure in several F2 populations tested and were assigned to rat chromosomes 17, 3, and 19, respectively. Endothelin receptor B cosegregated weakly with blood pressure and was provisionally assigned to rat chromosome 15. We conclude that, in the rat, one new blood pressure QTL is located on chromosome 5 marked by the ET2 locus and another new QTL is located on chromosome 17 near the HITH locus.