The maternal DDK syndrome phenotype is determined by modifier genes that are not linked to Om

The DDK syndrome is a polar, early embryonic lethal phenotype caused by incompatibility between a maternal factor of DDK origin and a paternal gene of non-DDK origin. Both maternal factor and paternal gene have been mapped to the Om locus on mouse Chromosome (Chr) 11. The paternal contribution to the syndrome has been shown to segregate as a single locus. Although the inheritance of the maternal contribution has not been characterized in depth, it as been assumed to segregate as a single locus. We have now characterized the segregation of the DDK fertility phenotype in over 240 females. Our results demonstrate that females require at least one DDK allele at Om to manifest the syndrome. However, the DDK syndrome inter-strain cross-fertility phenotype of heterozygous females is highly variable and spans the gamut from completely infertile to completely fertile. Our results indicate that this phenotypic variability has a genetic basis and that the modifiers of the DDK syndrome segregate independently of Om. Received: 24 November 1998 / Accepted: 19 January 1999     

Aged BALB/c mice as a model for increased severity of severe acute respiratory syndrome in elderly humans

Advanced age has repeatedly been identified as an independent correlate of adverse outcome and a predictor of mortality in cases of severe acute respiratory syndrome (SARS). SARS-associated mortality may exceed 50% for persons aged 60 years or older. Heightened susceptibility of the elderly to severe SARS and the ability of SARS coronavirus to replicate in mice led us to examine whether aged mice might be susceptible to disease. We report here that viral replication in aged mice was associated with clinical illness and pneumonia, demonstrating an age-related susceptibility to SARS disease in animals that parallels the human experience.     

Comparative effect of Neospora caninum infection in BALB/c mice at three different gestation periods

Neospora caninum has been recognized as a major cause of infectious bovine abortion worldwide. In the present study, the effect of N. caninum infection in mice at the 3 gestation periods (first, second, and third period) was investigated. In dams, tissue distribution of N. caninum was evaluated by nested polymerase chain reaction. In the progeny, fetal mortality, stillbirth, litter size, neonatal mortality/morbidity, vertical transmission, and parasite burden in neonatal tissues were evaluated. Pregnant BALB/c mice were infected subcutaneously with 2 x 10(6) NC-1 tachyzoites on days 0, 7, or 14 of gestation. Dams from each group were sequentially killed during gestation and postpartum (PP). Pups were killed on days 1 and 7 PP. Infection on day 0 of gestation produced a high vertical transmission rate, although no changes in fetal mortality, stillbirth, and littermate size were observed. The highest level of vertical transmission, together with an increase in fetal mortality and stillbirth and a decrease in litter size, were observed when infection was done on day 7 of gestation. Finally, infection on day 14 of gestation produced the lowest vertical transmission. Furthermore, infection at any time during gestation compromised the postnatal development of pups, because neonates from infected dams showed less body weight and a delay in the hair development.     

Maximum likelihood estimation of the frequency of null alleles at microsatellite loci

We review three methods for estimating the frequency of null alleles at codominant loci (such as microsatellite loci) and present a new maximum likelihood approach. Computer simulations show that the maximum likelihood estimator has a smaller root mean squared error than previous estimators.     

Toxoplasma gondii: Effect of maternal infection in the development of lymphoid organs of BALB/c neonates

Toxoplasmosis is one of the worldwide parasitic zoonoses. Alterations in the lymphopoietic system are still poorly studied. We analyzed lymphoid organs of BALB/c mice neonates from Toxoplasma gondii-intraperitoneally-infected mothers on 19th day of gestation, with 30 tachyzoites of strain RH. Normal non-infected pregnant females were used as controls. At 7 days after birth, animals were classified as neonates from infected (NIM) and neonates from non-infected mothers (NNIM). Weight of the thymus and number of thymic cells in NIM were decreased, percentage of apoptosis was significantly increased. Decrease in lymphocytes and monocytes and an increase of plasma cells were observed in bone marrow of NIM. Peripheral blood of NIM showed an increase of monocytes and neutrophils and a decrease in lymphocytes. Infection of the mother during the last day of gestation provokes in the neonates changes in the lymphoid organs that could explain survival of 75% of them.     

The effect of variable environments on polymorphism at loci with several alleles II. Submultiplicative viabilities

Circumstances assuring a unique stable equilibrium are investigated for a subdivided population with several alleles segregating at a single locus. For a broad class of selection regimes entailing heterozygote viabilities greater than the geometric mean of the corresponding homozygote viabilities, a stable fixation state precludes any other stable equilibria if either total-panmixia or temporal variation is operating. This extends known results for two alleles at a single locus and partially delimits when some of the bizarre behaviour engendered by multiple alleles may occur.Supported in part by National Science Foundation (USA) grant MCS-8002227     

"Silent" alleles at the HLA-C locus.

Defined specificities of the HLA-C locus possess a significantly lower immunogenicity as compared with the HLA-A and HLA-B specificities. HLA-C "blanks" are not immunogenic at all. Among the possible explanations, the most likely one appears to be a low phenotypic expression of these alleles. C locus antigens as a whole are thus likely to be of minor relevance in donor/recipient matching for transplantation.     

Number of alleles at the incompatibility loci in Secale cereale L.

Summary Two experiments were performed to estimate the number of alleles at the two incompatibility loci of rye in the variety Halo. In one experiment I₁ progenies from enforced selfing under controlled conditions were isolated. In the other experiment a genotype, homozygous at both incompatibility loci, was used as pollinator for a sample of the Halo population, which was regarded as an equilibrium population. Genotypes, which are homozygous at both incompatibility loci, can be found after selfing. The estimate for the number of alleles was 6 to 7 at one locus and 12 to 13 at the other locus.     

Rescue of the mouse DDK syndrome by parent-of-origin-dependent modifiers

When females of the DDK inbred mouse strain are mated to males of other strains, 90-100% of the resulting embryos die during early embryonic development. This DDK syndrome lethality results from incompatibility between an ooplasmic DDK factor and a non-DDK paternal gene, which map to closely linked loci on chromosome 11. It has been proposed that the expression of the gene that encodes the ooplasmic factor is subject to allelic exclusion in oocytes. Previous studies have demonstrated the existence of recessive modifiers that increase lethality in the C57BL/6 and BALB/c strains. These modifiers are thought to skew the choice of allele undergoing allelic exclusion in the oocytes of heterozygous females. In the present study, we demonstrate the presence of modifiers in three Mus musculus domesticus wild-derived strains, PERA, PERC, and RBA. These modifiers completely rescued DDK syndrome lethality. We mapped the major locus that is responsible for rescue in PERA and PERC crosses to proximal chromosome 13 and named this locus Rmod1 (Rescue Modifier of the DDK Syndrome 1). Our experiments demonstrate that PERA or PERC alleles at Rmod1 rescue lethality independently of allelic exclusion. In addition, rescue of the lethal phenotype depends on the parental origin of the Rmod1 alleles; transmission through the dam leads to rescue, while transmission through the sire has no effect.     

Leishmania chagasi: effect of the iron deficiency on the infection in BALB/c mice

Iron deficiency and visceral leishmaniasis are serious problems of public health. The aim of this study was to evaluate the effect of iron deficiency, induced by the iron chelator desferrioxamine, on the course of the infection by Leishmania chagasi in BALB/c mice. Our data show that the iron chelator caused significant reduction in hemoglobin concentration of treated mice and reduction in parasite load in spleen and liver. Significant differences were not observed in the production of IFN-gamma and IL-4 among the experimental groups. In conclusion, the data reported in this paper suggest that iron deficiency may favor the host. If there is not enough iron available to the parasite, its multiplication may be reduced and infection attenuated.     

Exact tests for association between alleles at arbitrary numbers of loci

Associations between allelic frequencies, within and between loci, can be tested for with an exact test. The probability of the set of multi-locus genotypes in a sample, conditional on the allelic counts, is calculated from multinomial theory under the hypothesis of no association. Alleles are then permuted and the conditional probability calculated for the permuted genotypic array. The proportion of arrays no more probable than the original sample provides the significance level for the test. An algorithm is provided for counting genotypes efficiently in the arrays, and the powers of the test presented for various kinds of association. The powers for the case when associations are generated by admixture of several populations suggest that exact tests are capable of detecting levels of association that would affect forensic calculations to a significant extent.     

Adjuvanticity effect of sodium alginate on subcutaneously injected BCG in BALB/c mice

Bacillus Calmette-Guerin (BCG) is the only available vaccine against tuberculosis. The research for an improved vaccine is currently a very active field of investigation. In the present study, adjuvanticity effect of sterile sodium alginate on subcutaneous BCG vaccination in BALB/c mice was investigated. Mice were vaccinated subcutaneously with BCG plus alginate and the immune response and protective effect were compared to those of mice vaccinated with BCG alone by the same route. Proliferative and delayed-type hypersensitivity responses, IFN-γ, specific anti-mycobacterium total IgG, IgG1 and IgG2a production were significantly higher in mice immunized subcutaneously with BCG plus alginate in comparison with results of mice immunized with BCG alone. Following systemic infection with BCG, mice vaccinated with BCG plus alginate had lower mean bacterial count compared to those vaccinated with BCG alone. The immune responses induced by subcutaneous administration of BCG plus alginate were significantly better than the responses induced by standard BCG vaccination.     

The effect of variable environments on polymorphism at loci with several alleles I. A symmetric model

Much of the extant polymorphism has been attributed to spatial and temporal variation among selection regimes. Analysis of models entailing two alleles at a single locus has demonstrated that polymorphism may result from variation among selection regimes which prescribe monomorphism if constant. This relationship is studied in the context of several alleles at a locus.One result which is not valid with only two alleles is that variation among selection regimes which specify polymorphic equilibria may lead to a stable monomorphic equilibrium. The analyses of temporal variation and total panmixia spatial variation among environments show that temporal variation allows the simultaneous stability of equilibrium configurations which cannot be simultaneously stable under total panmixia spatial variation (hard or soft selection). The principle that polymorphism is more readily maintained with spatial than temporal variation is invalidated.Supported in part by Purdue Research Foundation and National Science Foundation (USA) grant MCS-8002227     

Bacteriology of the oral cavity of BALB/c mice

To be used as a model in dental research, an animal must fulfil experimental needs and information on the composition and variation of its oral flora must be available. Only limited data are available on the indigenous oral bacterial flora of BALB/c mice. In this work, a total of 671 isolates from different sites (saliva, tongue, teeth, and mucosa) of the oral cavity of BALB/c mice were identified. Only 18 different species were isolated, which indicates the relative simplicity of the flora. The predominant species of the total cultivable flora were "Lactobacillus murinus" (38%), Staphylococcus aureus (37%), Streptococcus faecalis (8%), Staphylococcus sciuri (4%), and Escherichia coli (3%). The other species each represent less than 2% of the flora. "Lactobacillus murinus" is found in greater proportion on mucosa than in the other sites, Staph. aureus predominates in saliva, and Strep. faecalis was found in greater proportion in tooth samples. Statistical analyses, using the minimum percentage of similarity, indicate that there is some variation among the microflora of different mice but that this difference is smaller for mice from the same lot. These results set the basis for the study of the variations of the indigenous oral microflora of BALB/c mice under different conditions.     

Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome

Bardet-Biedl syndrome is a genetically and clinically heterogeneous disorder caused by mutations in at least seven loci (BBS1-7), five of which are cloned (BBS1, BBS2, BBS4, BBS6, and BBS7). Genetic and mutational analyses have indicated that, in some families, a combination of three mutant alleles at two loci (triallelic inheritance) is necessary for pathogenesis. To date, four of the five known BBS loci have been implicated in this mode of oligogenic disease transmission. We present a comprehensive analysis of the spectrum, distribution, and involvement in non-Mendelian trait transmission of mutant alleles in BBS1, the most common BBS locus. Analyses of 259 independent families segregating a BBS phenotype indicate that BBS1 participates in complex inheritance and that, in different families, mutations in BBS1 can interact genetically with mutations at each of the other known BBS genes, as well as at unknown loci, to cause the phenotype. Consistent with this model, we identified homozygous M390R alleles, the most frequent BBS1 mutation, in asymptomatic individuals in two families. Moreover, our statistical analyses indicate that the prevalence of the M390R allele in the general population is consistent with an oligogenic rather than a recessive model of disease transmission. The distribution of BBS oligogenic alleles also indicates that all BBS loci might interact genetically with each other, but some genes, especially BBS2 and BBS6, are more likely to participate in triallelic inheritance, suggesting a variable ability of the BBS proteins to interact genetically with each other.     

Nucleotide sequence of the BALB/c mouse beta-globin complex

The nucleotide sequence of 55,856 base-pairs containing all seven beta-globin homologous structures from chromosome 7 of the BALB/c mouse is reported. This sequence links together previously published sequences of the beta-globin genes, pseudogenes and repetitive elements. Using low stringency computer searches, we found no additional beta-globin homologous sequences, but did find many more long interspersed repetitive sequences (L1) than predicted by hybridization. L1 is a major component of the mouse beta-globin complex with at least 15 elements comprising about 22% of the reported sequence. Most open reading frames greater than 300 base-pairs in the cluster overlap with L1 repeats or globin genes. Polypurine, polypyrimidine and alternating purine/pyrimidine tracts are not evenly dispersed throughout the complex, but they do not appear to be excluded from or restricted to particular regions. Several regions of intergenic homology were detected in dot-plot comparisons of the mouse sequence with itself and with the human beta-globin sequence. The significance of these homologies is unclear, but these regions are candidates for further study in functional assays in erythroid cell lines or transgenic animals.