Various Inbred Strains Of Mice Research Articles

Genetic control of antibody responses induced by recombinant Mycobacterium bovis BCG expressing a foreign antigen.

Recombinant Mycobacterium bovis BCG expressing foreign antigens represents a promising candidate for the development of future vaccines and was shown in several experimental models to induce protective immunity against bacterial or parasitic infections. Innate resistance to BCG infection is under genetic control and could modify the immune responses induced against an antigen delivered by such engineered microorganisms. To investigate this question, we analyzed the immune responses of various inbred strains of mice to recombinant BCG expressing beta-galactosidase. These experiments demonstrated that BALB/c mice developed strong antibody responses against BCG expressing beta-galactosidase under the control of two different promoters. In contrast, C57BL/6, C3H, and CBA mice produced high anti-beta-galactosidase antibody titers only when immunized with recombinant BCG expressing beta-galactosidase under the control of the pblaF* promoter, which induced the production of high levels of this antigen. This difference in mouse responsiveness to recombinant BCG was not due to innate resistance to BCG infection, since similar immune responses were induced in Ity(r) and Ity(s) congenic strains of mice. In contrast, the analysis of anti-beta-galactosidase antibody responses of H-2 congenic mice in two different genetic backgrounds demonstrated that H-2 genes are involved in the immune responsiveness to beta-galactosidase delivered by recombinant BCG. Together, these results demonstrate that immune responses to an antigen delivered by recombinant BCG are under complex genetic influences which could play a crucial role in the efficiency of future recombinant BCG vaccines.

Regulation of lipoprotein metabolism by estrogen in inbred strains of mice occurs primarily by posttranscriptional mechanisms.

Estrogen protects against developing premature coronary artery disease. However, the mechanism of protective effects of estrogen still remains poorly understood. One mechanism by which estrogen can have protective effects appears to be through modulation of plasma lipoproteins. We showed that the mouse can be used as animal model to study estrogen-mediated synthesis and secretion of lipoproteins since, unlike the rat, the mouse does not up-regulate LDL receptors (Srivastava et al. [4]). Since inbred strains of mice differ in their genetic background and show differing responsiveness to dietary lipids, we examined how various inbred strains of mice respond to estradiol administration, and whether some mouse strains show responses similar to rats. 17beta-estradiol was administered to male mice from 15 different inbred strains, and the changes in plasma levels of lipids, apoB, apoAI, and apoE were examined. Total cholesterol decreased in all but one strain, apoAI levels decreased in all but 3 strains while apoB levels and apoB/apoAI ratios increased in all but 2 strains, suggesting that in contrast to rats, the apoB-containing lipoproteins increased relative to HDL in all strains of mice examined. Basal and estradiol-induced changes in total cholesterol were significantly correlated with changes in apoAI, but not apoB, reflecting the predominance of HDL over other lipoproteins in mouse plasma. The effects of estrogen on plasma apoE levels varied among various inbred strains of mice tested. Plasma apoE levels increased in seven strains treated with estrogen, and remained unchanged in the rest. To examine whether changes of plasma apoproteins are associated with the changes in the respective hepatic mRNA levels, apoAI, B and E mRNA were quantified by RNase protection assay. Hepatic apoE mRNA did not show correlation with either basal or post treatment plasma apoE levels in any of the strains. Similarly, most of the mouse strains did not show correlation of plasma apoAI and apoB levels with the corresponding hepatic mRNA levels. These results suggest that estrogen regulates plasma lipoprotein concentrations primarily by posttranscriptional mechanisms, and there were strain-related differences in the estrogen-mediated regulation of lipoprotein metabolism.

Genetic control of T cell replacing factor/interleukin-5 production

T lymphocytes, on stimulation with antigen, can produce many kinds of cytokines. T cell replacing factor/interleukin-5(TRF/IL-5) is a B cell growth and differentiation factor which is considered to be one of the molecules involved in T-B cell interaction for inducing B cells to antibody forming cells. In this study, we have examined TRF/IL-5, interleukin-2(IL-2) and macrophage activating factor (MAF) activity in the supernatant of mycobacterium tuberculosis primed and PPD stimulated T cells (PPD-factors) from various inbred strains of mice to find a relationship between cytokine production and genetic background. While IL-2 and MAF activities in C 3H/HeJ PPD-factors were similar to those in BALB/c and C 3H/HeN PPD-factors, TRF/IL-5 activity in C 3H/HeJ PPD-factors was much lower than those in BALB/c and C 3H/HeN PPD-factors. The LPS gene, which controls the B lymphocyte response to LPS and is defective in C 3H/HeJ mice, may be related to TRF/IL-5 production in T lymphocytes. In other words, defective TRF/IL-5 production in C 3H/HeJ may reflect a non-related function regulated by the LPS gene.

Genetic control of resistance to Mycoplasma pulmonis infection in mice

The differences in susceptibility of various inbred strains of mice to a highly pathogenic strain of Mycoplasma pulmonis CT (T2) has been known for some time. We assessed the genetic control of resistance to T2 infection. Tracheolung lavage samples and lungs of mice were assessed for T2 organisms after intratracheal injection of T2. We found that H-2b (C57BL/6 (B6) and H-2k B10.BR mice were resistant, whereas H-2b A.By, H-2k C3H/Bi, H-2k C3H/HeJ (C3H), and H-2b BALB.B mice were susceptible. We also typed individual B6C3F2 mice for H-2 and for resistance to T2 and observed that resistance to T2 infections is controlled by a single dominant gene not linked to H-2. Histologic examination revealed severe lung lesions typical of M. pulmonis infections in susceptible C3H mice, in contrast to minimal lung lesions in resistant B6 mice. No significant titers of local or systemic antimycoplasma antibodies were detected in either resistant or susceptible mice at 5 days postinfection. Macrophages taken from uninfected B6 or C3H mice failed to inhibit growth of T2 in vitro. However, macrophages from B6 mice did inhibit growth of T2 much better than C3H macrophages when harvested on day 5 of infection. Thus, there is an association between activation of macrophage bactericidal function and genetic resistance to growth of T2 organisms.

The Cellular Immune Response Against Yersinia enterocolitica in Different Inbred Strains of Mice: Evidence for an Important Role of T Lymphocytes

Resistance of mice against infection with Yersinia enterocolitica has been shown to be related neither to the Ity locus coding for resistance against infection with Salmonella typhimurium and other pathogens nor to the H-2 locus. From other mouse infection models, e.g., murine leishmaniasis, there is evidence that a different T cell-dependent regulation of the host immune response in various inbred strains of mice determines the susceptibility to the infectious agent. However, until recently, little was known about the cellular immune response against Y. enterocolitica. Thus, in a first approach we used the highly virulent Y. enterocolitica strain WA of serotype O:8 and different inbred strains of mice (C57 BL/6, Balb/c and athymic T cell-deficient C57 BL/6 nude mice) to investigate the cell-mediated immunity against parenteral infection. Comparison of the median lethal dose and of the net-bacterial growth in the spleens of infected mice indicated that Balb/c mice could be considered as Yersinia-susceptible whereas C57 BL/6 mice were relatively resistant. However, in contrast to normal C57 BL/6, athymic T cell-deficient C57 BL/6 nude mice have proved to be highly susceptible to Yersinia infection suggesting that T cells are required for the elimination of the pathogen. This conclusion was supported by histomorphological and immunohistological results indicating that T lymphocytes were present in Yersinia-induced tissue lesions. Moreover, the adoptive transfer of Yersinia-specific T cell lines and clones into naive animals mediated significant protection against the pathogen in both Yersinia-resistant C57 BL/6 and in Yersinia-susceptible Balb/c mice. These findings emphasize an important role of T lymphocytes in the host response against Y. enterocolitica infection.

Some cellular and pathophysiological correlates of the inflammatory effects of a synthetic immunomodulatory agent, muramyl dipeptide (MDP)

Acute, fully reversible paw edema was produced in mice after systemic administration of muramyl dipeptide (MDP, i.e. N-acetylmuramyl-L-alanyl-D-isoglutamine). Its stereoisomer N-acetylmuramyl-D-alanyl-D-isoglutamine (MDP-D,D) was much less effective. The swelling of paws occurred very soon (1 h) after MDP injection, reached the maximum severity at an interval of 6 h and declined afterwards. While no substantial quantitative differences were found in the sensitivity of the various inbred strains of mice to edemagenic activity of MDP, athymic nude mice were completely resistant to the induction of edema. Formation of edema was blocked by silica, indomethacin (partially also by nordihydroguaiaretic acid), monoclonal antibodies against T-cells and their TH-subpopulation. It is suggested that the MDP-induced edema is a macrophage- and T-cell-dependent, prostaglandin- (and partially leukotriene)-mediated acute reaction associated with increased vascular permeability. Possible engagement of immune/inflammatory cytokines like IL-1 has been discussed. The data support the view that this type of edema is a consequence of changes in the activity of important cellular components of the immune system.

A potential animal model for studying CF heterozygote advantage: genetic variation in theophylline-inducible colonic chloride currents among inbred strains of mice.

We have used Ussing chambers to measure chloride secretion by colonic segments (mucosa, muscularis, and serosa) from various inbred strains of mice. We found lower theophylline-induced Cl- secretion in the DBA/2J than in the C57BL/6J strain. Their F1 showed significantly higher levels of Cl- secretion than did the C57BL/6J parental strain while colonic segments from five recombinant inbred B x D lines ranged between the C57BL/6J and F1 values. No major component of the variation appeared to be associated with alleles of the met oncogene region of chromosome 6 or the H-2 region of chromosome 17.

T-cell-dependent popliteal lymph node reactions to platinum compounds in mice.

The requirements for sensitization to complex salts of platinum were investigated in a mouse model by means of the popliteal lymph node (PLN) assay. A single subcutaneous injection of dissolved hexachloroplatinates without adjuvant induced a vigorous primary immune reaction in the draining PLN. Dose-dependent lymph node activation was determined by an increase in both PLN weight and cellularity. In C57BL/6 mice, peak reactions were obtained around day 6 after administration of 90-180 nmol Na2[PtCl6] or (NH4)2[PtCl6] per animal. Mice primed to [PtCl6]2- mounted an enhanced response upon local restimulation with suboptimal doses of the same but not unrelated compounds, indicating a specific secondary response. T cells were required to elicit PLN reactions to [PtCl6]2-, because athymic nude mice completely failed to respond, in contrast to their +/nu littermates. Differences between various inbred strains of mice revealed that Pt-induced PLN responses are genetically controlled. Moreover, the immunogenicity of Pt salts in mice is not confined to hexachloroplatinates, but other compounds, such as the antineoplastic agent cis-dichlorodiamine platinum, are able to induce comparable PLN reactions.

Antigen‐Specific Immunoregulation and Autoimmune Thyroiditisa

1. Large Thy1+, CD8+ immunoregulatory cells were found in the thymus of mice 9-16 days after injection of soluble mouse thyroglobulin (without adjuvant). 2. Similar immunoregulatory cells appeared in the spleen 14-21 days after antigen administration suggesting that they were generated in the thymus and later migrated to the spleen. 3. The immunoregulatory cells were antigen-specific and attached to cognate antigen. 4. The degree of inhibition by the immunoregulatory cells differed among various inbred strains of mice and were virtually absent from SJL mice. 5. The regulatory function of the cells was strain specific in vitro and in vivo, and was restricted by both H-2 and non-H-2 haplotype. 6. By panning on antigen-coated plates, immunoregulatory cells were isolated and cell lines and clones with inhibitory function established.

The immunoadjuvant effect of soluble glucan derivatives in mice

We examined the effect of soluble derivatives of yeast glucan on the humoral immune response of various strains of inbred mice after administration of different doses according to various schedules. Glucan was injected i.v. or s.c. in a single dose or repeatedly. The immune response was examined by determining the titres of serum hemagglutinins against sheep erythrocytes (SRBC-Ab). The immunoadjuvant effect of glucan derivatives depends on the inbred strain used, on the dose of glucan, mode and time of administration with respect to antigen injection. The results have shown that the stimulatory effect of glucan derivatives occurred already after a single injection, the optimum dose being 10-20 mg/kg. Intravenous injection was more efficient than the subcutaneous one. In some cases, a slight increase of the spleen mass was observed.

A polymorphism affecting apolipoprotein A-II translational efficiency determines high density lipoprotein size and composition.

High density lipoproteins (HDL) are heterogeneous particles consisting of about equal amounts of lipid and protein that are thought to mediate the transport of cholesterol from peripheral tissues to liver. We show that a previously identified polymorphism affecting HDL electrophoretic mobility in mice is due to a monogenic variation controlling HDL size and apolipoprotein composition. Thus, the HDL particles of various inbred strains of mice exhibit a striking difference in the ratio fo the two major apolipoproteins of HDL, apoA-I and apoA-II. HDL particles in all strains examined contain an average of about five apoA-I molecules; however, whereas the strains with small HDL contain two to three apoA-II molecules per particle, the strains with large HDL contain about five apoA-II molecules per particle. This increase in the protein content of the large HDL is also accompanied by increased lipid content. The HDL size polymorphism and apoA-II levels cosegregate with the apoA-II structural gene on mouse chromosome 1, indicating that a mutation of the apoA-II gene locus is responsible. The rates of synthesis of apoA-II are increased in the strains with large HDL and high apoA-II levels as compared to the strains with small HDL and low apoA-II levels. On the other hand, the fractional catabolic rates of both apoA-I and apoA-II among the strains are very similar, confirming that apoA-II concentrations are controlled at the level of synthesis. Despite the difference in rates of apoA-II synthesis between strains, the apoA-II mRNA levels in the strains are not discernibly different, suggesting that a mutation of the apoA-II structural gene controls apoA-II translational efficiency. This was confirmed by translating apoA-II mRNA in vitro using a rabbit reticulocyte lysate system. Sequencing of apoA-II cDNA from the strains revealed a number of nucleotide substitutions, which may affect translational efficiency. We conclude that the assembly of apoA-II into HDL does not have a set stoichiometry but, rather, is controlled by the production of apoA-II. As apoA-II levels increase, the HDL particles become larger and acquire more lipid, but apoA-I content per particle remains unchanged. These studies with mice provide a model for the metabolic relationships between apoA-I, apoA-II, and HDL lipid in humans.

Correlation between the Vß4+CD8+ T-cell population and theH-2 d haplotype

The V beta 4+ T-cell population was examined with a newly established antibody, KT4, specific for V beta 4. Between 4.8% and 19.4% of CD3+ peripheral T cells from various inbred strains of mice or F1 hybrids expressed V beta 4. The CD4 T-cell population had higher numbers of V beta 4+ T cells (5.5%-20.6%) than the CD8 T-cell population (2.5%-10.7%). Deletion of certain V beta-expressing T cells due to the presence of the Mlsa antigen and/or the absence of certain Tcrb-V genes increased relative numbers of V beta 4+ T cells. The data suggest that V beta 4+ CD8+ T cells might be positively selected by H-2d molecules.

A new allele of the lpr locus, lprcg, that complements the gld gene in induction of lymphadenopathy in the mouse.

Several mice with generalized lymphadenopathy were found in the CBA/KlJms (CBA) colony maintained at our institute. A new mutant strain of mice that develop massive lymphoid hyperplasia at 100% incidence within 5 mo after birth was established by crossing these diseased mice. Genetic studies on lymphadenopathy were conducted in F1, F2, and backcross populations from crosses between mutant CBA (CBA-m) and various inbred strains of mice. The results supported the control of lymphadenopathy by a single autosomal recessive gene. Since C3H/He-gld/gld (C3H-gld), MRL/MpJ-lpr/lpr (MRL-lpr), and C3H/HeJ-lpr/lpr (C3H-lpr) mice develop the same type of lymphoid hyperplasia, allelism of the mutant gene with gld or lpr was tested by investigating lymphadenopathy in F1 and backcross populations from crosses between CBA-m and C3H-gld, MRL-lpr, or C3H-lpr mice. The gene was confirmed to be allelic with lpr but not with gld. Interestingly, however, the mutant gene interacted with gld to induce less severe lymphadenopathy. Thus, the mutant gene was named lprcg, an lpr gene complementing gld in induction of lymphoproliferation. The genetic conclusion was supported by the same profile of surface markers of lymphoid cells with gld/gld, lpr/lpr, lprcg/lprcg, lprcg/lpr, and +/gld +/lprcg genotypes, as well as by massive lymph node hyperplasia and high titers of autoantibodies in the first four genotypes, but slight hyperplasia and insignificant autoantibody production in the last. The discovery of lprcg provided strong genetic evidence for the parallels between anomalous phenotypes of gld and lpr, and CBA/KlJms-lprcg/lprcg mice will contribute to elucidation of the mechanism of induction of the same abnormal differentiation and functions of lymphocytes by gld and lpr.

Antigen-Specific Lymphocyte Proliferative Responses in Inbred Mice after Trichinella spiralis Infection

The in vitro antigen-specific lymphoproliferative response of spleen, mesenteric lymph node (MLN), and coeliac lymph node (CLN) cells taken from various strains of inbred mice infected with Trichinella spiralis was assessed. In most experiments cell populations were stimulated with excretory/secretory antigens (ESA) derived from adult and larval worms. Lymphoid cells collected 5-7 days postinfection were usually the most responsive to ESA as measured by [3H]thymidine uptake. Spleen cells were more responsive than either MLN or CLN cells. There was a correlation between in vitro ESA stimulation and worm rejection in strong- and weak-responder strains of mice. Spleen and MLN cells of NFS mice showed higher antigen-specific responsiveness, whereas the same cells from B10.BR (H-2k) and B10.Q (H-2q) strains of mice were less responsive. Among intermediate responder strains 2 patterns were observed. Spleen and MLN cells of BuB and DBA/1 mice responded more strongly than those of C3H mice. Dose-response experiments demonstrated that increasing the infective dose of larvae to the host usually increased subsequent in vitro antigen-specific lymphoproliferation. Furthermore, non-MHC-linked genes appear to be the primary determinant of antigen-specific T-cell-proliferative responses in inbred mice infected with T. spiralis.

Major histocompatibility complex – dependent T cell epitopes of lymphocytic choriomeningitis virus nucleoprotein and their protective capacity against viral disease

In mice the immune response to infection with lymphocytic choriomeningitis virus (LCMV), a member of the arenavirus family, is mainly based on the activity of cytotoxic T cells. The immunogenic epitopes of the viral nucleoprotein recognized by cytotoxic T cells in various inbred strains of mice were defined. These epitopes were located in H-2d and H-2q mice in the amino-terminal region and in H-2b mice in the carboxy-terminal region of the nucleoprotein. A detailed analysis with synthetic peptides allowed the definition of a common epitope of 9 amino acids in H-2d and H-2q mice and of about 15 amino acids in H-2b mice. These T cell epitopes were all recognized in association with H-2 D or L transplantation antigen. The protective capacity of recombinant vaccinia viruses expressing these epitopes was documented by assaying prevention of virus replication, protection against LCM and prevention of the local footpad swelling reaction. Thus, distinct T cell epitopes on the same internal viral protein mediate protection in a major histocompatibility complex-restricted manner.

Genetic control of the humoral response to cryptococcal capsular polysaccharide in mice

Cryptococcus neoformans is responsible for opportunistic infections in patients with cellular immune defects. However, C. neoformans-specific capsular polysaccharide antibodies have been shown to participate in host defenses during cryptococcosis. We investigated the humoral response after primary immunization in various inbred strains of mice and the genetic control. Our data strengthen the arguments for the T-independent type-2 nature of cryptococcal antigen, since CBA/N mice were unable to produce specific antibodies. They show that the influence of the genetic background is predominant for the good response with at least four independent autosomal genes governing this response, including an Igh control as reported for other polysaccharides. Immunization of intra-H-2 recombinant mice on a B10 background allowed us to identify a major histocompatibility complex control located in the subregion E alpha. The genetic control of antibody production following immunization with cryptococcal polysaccharide might explain the high variability of humoral responses during cryptococcosis.

An immunogenic antigen of murine Plasmodium yoelii 17X associates with class I MHC glycoproteins.

Reticulocytes infected with the non-lethal variant of Plasmodium yoelii 17X (PY17X-NL) express elevated levels of class I, but not class II, MHC Ag when compared with non-parasitized reticulocytes. In contrast, class I Ag are not detectable on erythrocytes parasitized by the lethal variant PY17X-L. In addition, the responder status of various inbred strains of mice to PY17X-NL has been shown to positively correlate with the levels of class I MHC antigens expressed on PY17X-NL parasitized red blood cells (PRBC). MHC Ag are known to restrict, or guide, immune responses. However, earlier studies have failed to demonstrate H-2 restricted activity in the effector arm of immunity to blood-stage murine malaria. Therefore, we have examined the induction of immunity by irradiated PY17X-NL PRBC. No MHC restriction was observed in the ability of PRBC to immunize recipients. However, using irradiated PRBC bearing low, intermediate or high levels of class I Ag we found that the levels, rather than haplotype, of class I Ag expressed on irradiated PRBC greatly influenced their ability to induce immunity. Furthermore, class I-associated parasite-directed Ag were isolated as an immunogenic complex with anti-class I MHC antibody. Such complexes induced immunity in vivo in the absence of adjuvant suggesting a biologically important mechanism by which non-lethal, reticulocytic forms of malarial parasites may immunize their hosts.

Genetic control of glycolipid expression

A polymorphic variation of sialic acid species of sialosyllactosylceramide was found in dog erythrocytes. The analysis of the glycolipids in the erythrocytes of the individual dogs in a family of a Japanese breed of dog, Shiba-Inu, showed that the expression of sialosyllactosylceramide containing N-glycolylneuraminic acid was an autosomal dominant trait over the expression of that containing N-acetylneuraminic acid. Polymorphic variations of major liver gangliosides were also found in various strains of inbred mice. The strains were classified into three groups; the first group possessed only II 3 Neu-Gc-LacCer, the second group possessed II 3NeuGc-GgOse 3Cer in addition to II 3NeuGc-LacCer and the third group possessed II 3NeuGc-GgOse 4Cer and II 3NeuGc,IV 3NeuGc-GgOse 4Cer as well as the above two gangliosides. By subjecting mice of these three groups to genetic analysis, the strain of the first group (WHT/Ht mice) was demonstrated to be a recessive homozygote which had a single autosomal defective gene making it unable to express N-acetylgalactosaminyltransferase activity to produce II 3NeuGc-GgOse 3Cer. The strains of the second group (BALB/c and C57BL/10 mice) were also demonstrated to be recessive homozygotes which had a single autosomal defective gene making them unable to express high enough level of galactosyltransferase activity to produce II 3NeuGc-GgOse 4Cer. By the analysis of gangliosides and the enzyme activity of H-2 congenic mice and mice produced by a mating, this defective gene controlling the expression of II 3NeuGc-GgOse 4Cer through the regulation of the transferase activity was demonstrated to be linked to H-2 complex on chromosome 17.

Functional Competence of Dendritic Cells of Ageing C57BL/6 Mice

Highly polymorphic age-dependent differences in progression of T and B cells have been found in various strains of inbred mice. In the immune system of C57BL/6 mice these occur first in B cells and, later in life, in T cells. In this paper, we have examined the progression in the functional capacity of C57BL/6 dendritic cells (DC). Age-dependent changes were found in the syngeneic mixed leucocyte reaction, in which the stimulatory capacity of DC increased with age. This increase was independent of the age of the donor of the serum that was added to the culture, and occurred when young donors provided the T cells. Age-dependent changes in DC properties were not detected in terms of direct plaque-forming response, response to concanavalin A, or in the allogeneic mixed leucocyte reaction.

Genetic control of natural resistance to nontuberculous mycobacterial infections in mice.

Results show that various inbred strains of mice can be segregated into two distinct groups, based on their capacity to allow a number of nontuberculous mycobacterial infections to grow in target organs following experimental intravenous infection. The first group, which allowed these infections to grow progressively, was thus designated as naturally susceptible to these infections; in contrast, those strains which were able to exert detectable bacteriostasis were designated as naturally resistant. It was then found that segregation of mouse strains based on this distinction also mirrored the capacity of these animals to generate acquired immunity to the mycobacterial infections. For example, Mycobacterium simiae grew progressively in susceptible C57BL/6 mice, subsequently triggering acquired mechanisms of immunity, whereas no evidence for acquired immunity could be found in resistant A/Tru mice infected with this organism. The possibility that acquired immunity could not be expressed in the latter strain as a result of a defect in macrophage activation was excluded. Moreover, it was found that the trait of resistance to these infections could be transferred by bone marrow cells into radiation chimeras, thus indicating that this trait was expressed by the progeny of hemopoietic precursor cells. Subsequent backcross analysis to determine the mode of inheritance of the trait of resistance to these mycobacterial infections revealed data that were consistent with the hypothesis that this resistance is controlled by more than one gene. Statistical analysis of the data by the maximum likelihood method suggested polygenic control, although in some cases the probability values suggested control by a major gene, influenced by modifier genes. These findings suggest that the previous hypothesis that the growth of mycobacterial infections in inbred strains of mice is controlled by a single gene should be reevaluated.