Localization of Eutr2, a locus controlling susceptibility to DES-induced uterine inflammation and pyometritis, to RNO5 using a congenic rat strain

In some rat strains chronic administration of exogenous estrogens induces pyometritis, an inflammation of the uterus associated with infection, suggesting that there is genetic variation in susceptibility to estrogen-induced inflammation and pyometritis. In this article we report that following 10 weeks of treatment with the synthetic estrogen diethylstilbestrol (DES), Fisher 344 (F344) rats exhibit modest uterine inflammation and a 0% incidence of pyometritis. By contrast, under identical experimental conditions, Brown Norway (BN) rats exhibit significant inflammation and a 100% incidence of pyometritis. Similarly, we also observed profound uterine inflammation and a 100% incidence of pyometritis in a congenic rat strain in which a segment of RNO5 from the BN strain is carried on the F344 strain. These data suggest that a locus on RNO5 controls both the magnitude of DES-induced uterine inflammation and susceptibility to DES-induced pyometritis. This locus, designated Eutr2, resides within the same segment of RNO5 as the Eutr1 locus, which confers susceptibility to E2-induced pyometritis in an F2 population generated in a cross between the BN and August × Copenhagen 9935, Irish (ACI) strains. Jyotsna Pandey, Karen A. Gould contributed equally to this work.     

Genetic control of estrogen action in the rat: mapping of QTLs that impact pituitary lactotroph hyperplasia in a BN × ACI intercross

Estrogens are important regulators of growth and development and contribute to the etiology of several types of cancer. Different inbred rat strains exhibit marked, cell-type-specific differences in responsiveness to estrogens as well as differences in susceptibility to estrogen-induced tumorigenesis. Regulation of pituitary lactotroph homeostasis is one estrogen-regulated response that differs dramatically between different inbred rat strains. In this article we demonstrate that the growth response of the anterior pituitary gland of female ACI rats to 17β-estradiol (E2) markedly exceeds that of identically treated female Brown Norway (BN) rats. We further demonstrate that pituitary mass, a surrogate indicator of absolute lactotroph number, behaves as a quantitative trait in E2-treated F₂ progeny generated in a genetic cross originating with BN females and ACI males. Composite interval mapping analyses of the (BN×ACI)F₂ population revealed quantitative trait loci (QTLs) that exert significant effects on E2-induced pituitary growth on rat chromosome 4 (RNO4) (Ept5) and RNO7 (Ept7). Continuous treatment with E2 rapidly induces mammary cancer in female ACI rats but not BN rats, and QTLs that impact susceptibility to E2-induced mammary cancer in the (BN×ACI)F₂ population described here have been mapped to RNO3 (Emca5), RNO4 (Emca6), RNO5 (Emca8), RNO6 (Emca7), and RNO7 (Emca4). Ept5 and Emca6 map to distinct regions of RNO4. However, Ept7 and Emca4 map to the same region of RNO7. No correlation between pituitary mass and mammary cancer number at necropsy was observed within the (BN×ACI)F₂ population. This observation, together with the QTL mapping data, indicate that with the exception of the Ept7/Emca4 locus on RNO7, the genetic determinants of E2-induced pituitary growth differ from the genetic determinants of susceptibility to E2-induced mammary cancer.     

Genetic mapping of loci controlling diethylstilbestrol-induced thymic atrophy in the Brown Norway rat

Chronic estrogen administration can lead to thymic atrophy in rodents. In this article we report that the Brown Norway (BN) rat is sensitive to thymic atrophy induced by the estrogen diethylstilbestrol (DES). By contrast, DES does not induce significant thymic atrophy in the August × Copenhagen-Irish (ACI) strain. The sensitivity of the BN rat to DES-induced thymic atrophy appears to segregate as an incompletely dominant trait in crosses between the BN and ACI strains. In a (BN × ACI)F₂ population, we find strong evidence for three major genetic determinants of sensitivity to DES-induced thymic atrophy on rat Chromosome (RNO) 10 and RNO2. Genotypes at these loci, termed Esta1, 2, and 3, do not have a significant impact on the ability of DES to induce pituitary tumorigenesis or inhibit growth of these F₂ rats. These data indicate that the genetic factors that control DES-induced thymic atrophy are distinct from those that control the effects of DES on pituitary mass and body mass. The Esta intervals on RNO10 and RNO2 overlap with loci that control sensitivity to radiation-induced thymocyte apoptosis, as well as susceptibility to a variety of allergic and autoimmune pathologies, including allergic encephalitis, arthritis, and glomerulonephritis in rodents. These observations suggest that common genetic determinants may control sensitivity to estrogen-induced thymic atrophy, maintenance of thymocyte homeostasis, and immune function.     

Mapping diabetes QTL in an intercross derived from a congenic strain of the Brown Norway and Goto-Kakizaki rats

Genetic studies in experimental crosses derived from the inbred Goto-Kakizaki (GK) rat model of spontaneous diabetes mellitus have identified quantitative trait loci (QTL) for diabetes phenotypes in a large region of rat Chromosome (RNO) 1. To test the impact of GK variants on QTL statistical and biological features, we combined genetic and physiologic studies in a cohort of F₂ hybrids derived from a QTL substitution congenic strain (QTLSCS) carrying a 110-cM GK haplotype of RNO1 introgressed onto the genetic background of the Brown Norway (BN) strain. Glucose intolerance and altered insulin secretion in QTLSCS rats when compared with BN controls were consistent with original QTL features in a GK × BN F₂ cross. Segregating GK alleles in the QTLSCS F₂ cross account for most of these phenotypic differences between QTLSCS and BN rats. However, significant QTL for diabetes traits in both the QTLSCS and GK × BN F₂ cohorts account for a similar small proportion of their variance. Comparing results from these experimental systems provides indirect estimates of the contribution of genetic interactions and environmental factors to QTL architecture as well as locus and biological targets for future post-QTL mapping studies in congenic substrains. Electronic Supplementary Material Electronic Supplementary material is available for this article at and accessible for authorised users. Stephan C. Collins and Robert H. Wallis contributed equally to this work.     

Genetic bases of renal agenesis in the ACI rat: mapping of Renag1 to chromosome 14

Unilateral renal agenesis (URA) is a common developmental defect in humans, occurring at a frequency of approximately 1 in 500–1000 births. Several genetic syndromes include bilateral or unilateral renal agenesis as an associated phenotype. However, URA frequently occurs in individuals not afflicted by these syndromes and is often asymptomatic. Although it is clear that genetic factors contribute to the etiology of URA, the genetic bases of URA are poorly defined at this time. ACI rats, both males and females, exhibit URA at an incidence of 5%–15%. In this article we characterize the incidence of URA in female and male F₁, F₂, and backcross (BC) progeny from reciprocal genetic crosses between the ACI strain and the unaffected Brown Norway (BN) strain. Through interval mapping analyses of 353 phenotypically defined female F₂ progeny, we mapped to rat Chromosome 14 (RNO14) a genetic locus, designated Renag1 (Renal agenesis 1), that serves as the major determinant of URA in these crosses. Further genotypic analyses of URA-affected female and male F₂ and BC progeny localized Renag1 to a 14.4-Mb interval on RNO14 bounded by markers D14Rat50 and D14Rat12. The data from these genetic studies suggest that the ACI allele of Renag1 acts in an incompletely dominant and incompletely penetrant manner to confer URA. James D. Shull and Cynthia M. Lachel authors contributed equally to this work.     

The mutation of the LEW.1AR1-<Emphasis Type="Italic">iddm</Emphasis> rat maps to the telomeric end of rat chromosome 1

The LEW.1AR1-iddm rat is an animal model of human type 1 diabetes mellitus (T1DM) with an autosomal recessive mode of inheritance. T1DM susceptibility loci could be localized on chromosome (RNO) 20 in the major histocompatibility complex region (Iddm1) and on RNO1 (Iddm8, Iddm9) in a BN backcross cohort. In this study the impact of the different susceptibility regions on diabetes development was investigated in a backcross population of the diabetes-resistant PAR strain. A cohort of 130 [(PAR × LEW.1AR1-iddm) × LEW.1AR1-iddm] N2 rats was monitored for blood glucose and analyzed by linkage analysis. Sixteen percent of the PAR backcross animals developed T1DM. Genetic analysis revealed significant linkage to T1DM in the MHC region on RNO20p12. In contrast to the linkage analysis of the BN backcross cohort, only one susceptibility locus for T1DM could be identified on RNO1. This susceptibility region on RNO1 mapped to the telomeric end corresponding to Iddm8. Eighty-nine percent of diabetic PAR backcross animals were homozygous for Iddm8. The Iddm9 diabetes susceptibility region showed no linkage to diabetes in the PAR backcross cohort. The data of this study provide evidence that the mutation leading to T1DM in the LEW.1AR1-iddm rat is located at the telomeric end of RNO1 corresponding to Iddm8. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. H. Weiss and T. Arndt contributed equally to this study.     

Genomic assignment of the warfarin resistance locus, Rw, in the rat

The locus responsible for resistance to the anticoagulants warfarin and bromadiolone (locus symbol Rw) was integrated into the rat (Rattus norvegicus) microsatellite genome map. Seventh-generation offspring of a segregating strain of rats heterozygous resistant to both compounds were tested with a blood-clotting-response (BCR) test. No recombination between resistance to warfarin and bromadiolone was observed, indicating a common genetic basis. No recombinants were found between Rw and D1Arb18 (Myl2) located at the MIT-microsatellite map position 95.90 (SHRSP × BN F₂-cross) or 82.24 (FHH × ACI F₂-cross). Resistance segregated in a ratio expected for single, dominant gene responses. An equal number of females and males were resistant, but females retained higher percentage blood coagulation activities (PCA) after anticoagulant administration. Partial synteny between rat, mouse, and human suggests that Myl2 may serve as anchor to map the Rw homologs in mouse and human. Received: 30 December 1998 / Accepted: 17 March 1999     

A rat homolog of the mouse deafness mutant jerker (je)

An autosomal recessive deafness mutant was discovered in our colony of Zucker (ZUC) rats. These mutants behave like shaker-waltzer deafness mutants, and their inner ear pathology classifies them among neuroepithelial degeneration type of deafness mutants. To determine whether this rat deafness mutation (−) defines a unique locus or one that has been previously described, we mapped its chromosomal location. F₂ progeny of (Pbrc:ZUC × BN/Crl) A/a B/b H/h+/− F₁ rats were scored for coat color and behavioral phenotypes. Segregation analysis indicated that the deafness locus might be loosely linked with B on rat Chromosome (Chr) 5 (RNO5). Therefore, 40 −/− rats were scored for BN and ZUC alleles at four additional loci, D5Mit11, D5Mit13, Oprd1, and Gnb1, known to map to RNO5 or its homolog, mouse Chr 4 (MMU4). Linkage analysis established the gene order (cM distance) as D5Mit11–(19.3)–B–(17.9)–D5Mit13–(19.2)–Oprd1–(21.5) − (1.2) Gnb1, placing the deafness locus on distal RNO5. The position of the deafness locus on RNO5 is similar to that ofjerker (je) on MMU4; the phenotypes and patterns of inheritance of the deafness mutation and je are also similar. It seems likely that the mutation affects the rat homolog of je. The rat deafness locus should, therefore, be named jerker and assigned the gene symbol Je. Received: 13 June 1995 / Accepted: 4 January 1996     

Genetic dissection of ``OLETF', a rat model for non-insulin-dependent diabetes mellitus

To elucidate the genetic factors underlying non-insulin-dependent diabetes mellitus (NIDDM), we performed genome-wide quantitative trait locus (QTL) analysis, using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The OLETF rat is an excellent animal model of NIDDM because the features of the disease closely resemble human NIDDM. Genetic dissection with two kinds of F2 intercross progeny, from matings between the OLETF rat and non-diabetic control rats F344 or BN, allowed us to identify on Chromosome (Chr) 1 a major QTL associated with features of NIDDM that was common to both crosses. We also mapped two additional significant loci, on Chrs 7 and 14, in the (OLETF × F344)F₂ cross alone, and designated these three loci as Diabetes mellitus, OLETF type Dmo 1, Dmo2 and Dmo3 respectively. With regard to suggestive QTLs, we found loci on Chrs 10, 11, and 16 that were common to both crosses, as well as loci on Chrs 5 and 12 in the (OLETF × F344)F₂ cross and on Chrs 4 and 13 in the (OLETF × BN)F₂ cross. Our results showed that NIDDM in the OLETF rat is polygenic and demonstrated that different genetic backgrounds could affect ``fitness' for QTLs and produce different phenotypic effects from the same locus. Received: 9 October 1997 / Accepted: 29 January 1998     

QTL mapping for traits associated with stress neuroendocrine reactivity in rats

In the present study we searched for quantitative trait loci (QTLs) that affect neuroendocrine stress responses in a 20-min restraint stress paradigm using Brown–Norway (BN) and Wistar–Kyoto–Hyperactive (WKHA) rats. These strains differed in their hypothalamic–pituitary–adrenal axis (plasma ACTH and corticosterone levels, thymus, and adrenal weights) and in their renin–angiotensin–aldosterone system reactivity (plasma renin activity, aldosterone concentration). We performed a whole-genome scan on a F₂ progeny derived from a WKHA × BN intercross, which led to the identification of several QTLs linked to plasma renin activity (Sr6, Sr8, Sr11, and Sr12 on chromosomes RNO2, 3, 19, and 8, respectively), plasma aldosterone concentration (Sr7 and Sr9 on RNO2 and 5, respectively), and thymus weight (Sr10, Sr13, and Srl4 on RNO5, 10, and 16, respectively). The type 1b angiotensin II receptor gene (Agtrlb) maps within the confidence intervals of QTLs on RNO2 linked to plasma renin activity (Sr6, highly significant; LOD = 5.0) and to plasma aldosterone level (Sr7, suggestive; LOD = 2.0). In vitro studies of angiotensin II–induced release of aldosterone by adrenal glomerulosa cells revealed a lower receptor potency (log EC₅₀ = −8.16 ± 0.11 M) and efficiency (E_max = 453.3 ± 25.9 pg/3 × 10⁴ cells/24 h) in BN than in WKHA (log EC₅₀ = −10.66 ± 0.18 M; E_max = 573.1 ± 15.3 pg/3 × 10⁴ cells/24 h). Moreover, differences in Agtr1b mRNA abundance and sequence reinforce the putative role of the Agtr1b gene in the differential plasma renin stress reactivity between the two rat strains.     

Genetic analysis of the LEW.1AR1-iddm rat: an animal model for spontaneous diabetes mellitus

The LEW.1AR1-iddm/Ztm rat is a new animal model of type 1 diabetes mellitus, which shows an autosomal recessive mode of inheritance for the diabetes-inducing gene. The aim of this study was to define predisposing loci of the diabetic syndrome by linkage analysis using microsatellite markers. A backcross population of 218 rats (BN × LEW.1AR1-iddm) × LEW.1AR1-iddm was analyzed using 157 polymorphic microsatellite markers covering the entire genome. Three genomic regions showed a significant linkage to the diabetic syndrome. The first susceptibility locus on rat Chromosome (RNO) 1 (LOD score 4.13) mapped to the region 1q51–55, which codes for potential candidate genes like Ins1 and Nkx2-3. The second susceptibility locus was also localized on RNO1 in the centromeric region 1p11 (LOD score 2.7) encompassing the Sod2 gene. The third quantitative trait loci (LOD score 2.97) was located on RNO20 within the major histocompatibility complex region. Comparative mapping revealed that the homologous regions in the human genome contain the IDDM loci 1, 5, 8, and 17. The identification of diabetes susceptibility regions of the genetically uniform LEW.1AR1-iddm rat strain will pave the way toward a detailed characterization of the loci conferring diabetes development as well as their functional relevance for the pathogenesis of type 1 diabetes mellitus.     

An integrated genetic linkage map of the laboratory rat

The laboratory rat, Rattus novegicus, is a major model system for physiological and pathophysiological studies, and since 1966 more than 422,000 publications describe biological studies on the rat (NCBI/Medline). The rat is becoming an increasingly important genetic model for the study of specific diseases, as well as retaining its role as a major preclinical model system for pharmaceutical development. The initial genetic linkage map of the rat contained 432 genetic markers (Jacob et al. 1995) out of 1171 developed due to the relatively low polymorphism rate of the mapping cross used (SHR × BN) when compared to the interspecific crosses in the mouse. While the rat genome project continues to localize additional markers on the linkage map, and as of 11/97 more than 3,200 loci have been mapped. Current map construction is using two different crosses (SHRSP × BN and FHH × ACI) rather than the initial mapping cross. Consequently there is a need to provide integration among the different maps. We set out to develop an integrated map, as well as increase the number of markers on the rat genetic map. The crosses available for this analysis included the original mapping cross SHR × BN reciprocal F2 intercross (448 markers), a GH × BN intercross (205 markers), a SS/Mcw × BN intercross (235 markers), and a FHH/Eur × ACI/Hsd intercross (276 markers), which is also one of the new mapping crosses. Forty-six animals from each cross were genotyped with markers polymorphic for that cross. The maps appear to cover the vast majority of the rat genome. The availability of these additional markers should facilitate more complete whole genome scans in a greater number of strains and provide additional markers in specific genomic regions of interest. Received: 3 December 1997 / Accepted: 20 February 1998     

Genetic determination of susceptibility to estrogen-induced mammary cancer in the ACI rat: mapping of Emca1 and Emca2 to chromosomes 5 and 18

Hormonal, genetic, and environmental factors play major roles in the complex etiology of breast cancer. When treated continuously with 17beta-estradiol (E2), the ACI rat exhibits a genetically conferred propensity to develop mammary cancer. The susceptibility of the ACI rat to E2-induced mammary cancer appears to segregate as an incompletely dominant trait in crosses to the resistant Copenhagen (COP) strain. In both (ACI x COP)F(2) and (COP x ACI)F(2) populations, we find strong evidence for a major genetic determinant of susceptibility to E2-induced mammary cancer on distal rat chromosome 5. Our data are most consistent with a model in which the ACI allele of this locus, termed Emca1 (estrogen-induced mammary cancer 1), acts in an incompletely dominant manner to increase both tumor incidence and tumor multiplicity as well as to reduce tumor latency in these populations. We also find evidence suggestive of a second locus, Emca2, on chromosome 18 in the (ACI x COP)F(2) population. The ACI allele of Emca2 acts in a dominant manner to increase incidence and decrease latency. Together, Emca1 and Emca2 act independently to modify susceptibility to E2-induced mammary cancer.     

The circling behavior of the deafblind LEW-<Emphasis Type="Italic">ci2</Emphasis> rat is linked to a segment of RNO10 containing <Emphasis Type="Italic">Myo15</Emphasis> and <Emphasis Type="Italic">Kcnj12</Emphasis>

The LEW/Ztm-ci2 rat is an autosomal recessive mutant that displays circling behavior, deafness, progressive retinopathy, locomotor hyperactivity, ataxia, and opisthotonus. We performed a genome-wide scan of a (LEW/Ztm-ci2 × BN/Ztm) F₁ × LEW/Ztm-ci2 backcross population with anonymous microsatellite markers to analyze the genetics of this mutant rat. This linkage analysis demonstrated a very strong association of RNO10 SSLP markers to the phenotype with a core region in the central part of the chromosome. The knowledge of genes mapping to this part of the rat genome and their linkage to SSLP markers is still poor. We developed SSLP markers closely linked to genes, which might be responsible for the mutant phenotype by using the growing amount of rat-specific DNA sequences available at World Wide Web databases. Application of this method facilitated the search for candidate genes for the phenotype of the LEW-ci2 rat. We were able to map Myo15 and its neighboring genes, Znf179 and Aldh3a1, to the region of interest and Myo1c to a more distal location on RNO10. Further rat BAC clones were used to create a physical map of the region of interest. This map revealed the position of further genes. Among those is Kcnj12. Owing to their localization on RNO10 and their involvement in a similar pathology in human and mouse, Myo15 and Kcnj12 can be regarded as candidate genes for the deafblind phenotype of the LEW-ci2 rat.     

Genetic Etiology of Renal Agenesis: Fine Mapping of Renag1 and Identification of Kit as the Candidate Functional Gene

Congenital anomalies of the kidney and urogenital tract (CAKUT) occur in approximately 0.5% of live births and represent the most frequent cause of end-stage renal disease in neonates and children. The genetic basis of CAKUT is not well defined. To understand more fully the genetic basis of one type of CAKUT, unilateral renal agenesis (URA), we are studying inbred ACI rats, which spontaneously exhibit URA and associated urogenital anomalies at an incidence of approximately 10%. URA is inherited as an incompletely dominant trait with incomplete penetrance in crosses between ACI and Brown Norway (BN) rats and a single responsible genetic locus, designated Renag1, was previously mapped to rat chromosome 14 (RNO14). The goals of this study were to fine map Renag1, identify the causal genetic variant responsible for URA, confirm that the Renag1 variant is the sole determinant of URA in the ACI rat, and define the embryologic basis of URA in this rat model. Data presented herein localize Renag1 to a 379 kilobase (kb) interval that contains a single protein coding gene, Kit (v-kit Hardy-Zukerman 4 feline sarcoma viral oncogene homolog); identify an endogenous retrovirus-derived long terminal repeat located within Kit intron 1 as the probable causal variant; demonstrate aberrant development of the nephric duct in the anticipated number of ACI rat embryos; and demonstrate expression of Kit and Kit ligand (Kitlg) in the nephric duct. Congenic rats that harbor ACI alleles at Renag1 on the BN genetic background exhibit the same spectrum of urogenital anomalies as ACI rats, indicating that Renag1 is necessary and sufficient to elicit URA and associated urogenital anomalies. These data reveal the first genetic link between Kit and URA and illustrate the value of the ACI rat as a model for defining the mechanisms and cell types in which Kit functions during urogenital development.     

Pas1 is a common lung cancer susceptibility locus in three mouse strains

Inherited predisposition to lung cancer is a phenotypic trait shared by different mouse inbred strains that show either a high or an intermediate predisposition. Other strains are instead genetically resistant. The Pas1 locus is the major determinant of lung cancer predisposition in the A/J strain (Gariboldi et al. 1993). To define the determinants of susceptibility to lung tumorigenesis in the highly susceptible SWR/J and in the intermediately susceptible BALB/c mice, we analyzed (BALB/c × SWR/J)F₂ and (BALB/c × C3H/He)F₂ crosses by genetic linkage experiments. The present results provide unequivocal evidence that the same Pas1/+ allele that leads to lung cancer predisposition is shared by A/J, SWR/J, and BALB/c strains. The intermediate susceptibility of the BALB/c strain would result by interaction of Pas1 locus with lung cancer resistance loci. Received: 18 April 1997 / Accepted: 15 June 1997     

Inheritance of resistance to anti-microtubule dinitroaniline herbicides in an “intermediate” resistant biotype of Eleusine indica (Poaceae)

Inheritance of resistance to the anti-microtubule dinitroaniline herbicides was investigated in a goosegrass biotype displaying an intermediate level of resistance (I). Reciprocal crosses were made between the I biotype and previously characterized susceptible (S) or resistant (R) biotypes. Eight F₁ hybrids were identified, and F₂ populations were produced by selfing. The dinitroaniline-herbicide response phenotype (DRP) of F₁ plants, and F₂ seedlings was determined using a root-growth bioassay. The DRP of F₁ plants of S × I was “susceptible” (i.e., identical to the S parental plants), and the DRP of F₁ plants of I × R was “intermediate” (i.e., identical to the I parental plants). Nonparental phenotypes were not observed in F₁ plants. Results indicated susceptibility to be dominant over intermediate resistance and intermediate resistance to be dominant over high resistance. Analysis of reciprocal crosses ruled out any role for cytoplasmic inheritance. When treated at the discriminating concentration (e.g., 0.28 ppm oryzalin), F₂ seedlings of S × I were classified as either S or I phenotype, and F₂ seedlings of I × R were classified as either I or R phenotype. Again, nonparental phenotypes were not observed. The 3:1 (S:I or I:R) segregation ratios in F₂ seedlings were consistent across all eight F₂ families. The results show that dinitroaniline herbicide resistance in the I biotype of goosegrass is inherited as a single, nuclear gene. Furthermore, it suggests that dinitroaniline resistance in goosegrass is controlled by three alleles at a single locus (i.e., Drp-S, Drp-i, and Drp-r).     

Spontaneous polyploidy,gynogenesis and androgenesis in second generation (F2) koi Cyprinus carpio × goldfish Carassius auratus hybrids

The objective of this study was to characterize the genetics of second generation (F₂) koi Cyprinus carpio × goldfish Carassius auratus hybrids. Spermatozoa produced by a novel, fertile F₁ male were found to be diploid by flow‐cytometric analysis. Backcross (F₁ female × C. carpio male and C. carpio female × F₁ male) juveniles were triploid, confirming that female and male F₁ hybrids both produced diploid gametes. The vast majority of surviving F₂ juveniles was diploid and small proportions were aneuploid (2·1n–2·3n and 3·1n–3·9n), triploid (3n) and tetraploid (4n). Microsatellite genotyping showed that F₂ diploids repeated either the complete maternal or the complete paternal genotype. Fish with the maternal genotype were female and fish with the paternal genotype were male. This demonstrates that F₂ diploids were the result of spontaneous gynogenesis and spontaneous androgenesis. Analysis of microsatellite inheritance and the sex ratio in F₂ crosses showed that spontaneous gynogenesis and androgenesis did not always occur in equal proportions. One cross was found to have an approximate equal number of androgenetic and gynogenetic offspring while in several other crosses spontaneous androgenesis was found to occur more frequently than spontaneous gynogenesis.     

Cytogenetical studies on artificial hybrids amongElymus sibiricus,E. dahuricus andAgropyron tsukushiense in the tribe Triticeae,Gramineae

To explore the cytogenetical relationships ofElymus andAgropyron of the tribe Triticeae, Gramineae, two species of AsiaticElymus, E. sibiricus (2n=28) andE. dahuricus (2n=42), and a JapaneseAgropyron, A. tsukushiense (2n=42) were crossed. Pentaploid and hexaploid F₁ hybrids were vigorous. All pollen grains were aborted and none of the hybrids produced seed. For the crossE. sibiricus × A. tsukushiense, the average chromosome pairing per cell at the MI of the PMCs in the F₁ was 16.38 univalents, 8.93 bivalents, 0.25 trivalents and 0.01 quadrivalents; for the crossE. dahuricus × A. tsukushiense, it was 4.41 univalents, 17.67 bivalents, 0.32 trivalents, 0.28 quadrivalents and 0.04 quinquevalents; and for the crossE. dahuricus × E. sibiricus, it was 17.11 univalents, 8.74 bivalents, 0.04 trivalents and 0.07 quadrivalents. From the present results, it is concluded thatE. sibiricus contains one genome andE. dahuricus contains two genomes, which are homologous to those ofA. tsukushiense, and that the third genome ofE. dahuricus might be partially homologous to the remaining genome ofA. tsukushiense. This conclusion is also supported by the cytogenetical analysis ofE. dahuricus × E. sibiricus. Contribution No. 27 from the Plant Germ-plasm Institute, Faculty of Agriculture, Kyoto University, Kyoto, Japan.     

TheRT1.G locus in the rat encodes a Qa/TL-like antigen

A new antigenic system in the rat homologous to theQa/TL antigen system in the mouse has been characterized. It was detected by antibodies raised in donor-recipient combinations that were matched for theRT1. A, B, D, E loci in the major histocompatibility complex (MHC): (R11×BN)F₁ anti-BN.1L(LEW), (R18×BN)F₁ anti-BN.1L, and BN.1LV1(F344) anti-BN.1L. Absorption analyses using these antisera and a variety of inbred, congenic and recombinant strains identified three alleles,RT1.G ^a ,G ^b ,G ^c , of whichG ^c is a null allele. The strain distribution of these alleles was determined, using 37 strains of rats representative of all of the prototypic haplotypes and a number of congenic and recombinant strains. The use of the congenic and recombinant strains showed that theRT1.G locus was linked to the MHC and that the most probable gene order wasA-E-G. Testcross analysis showed that the map distance betweenA andG was 1.4 cM(4/285 recombinants). The RT1.G antigen has a heavy chain ofM _r 46 000 and is present on both T and B cells.