Microbial Pathogenesis 1992 ; 13 : 157-160
Short communication Genetic control of resistance to enterotoxigenic Escherichia co/i in infant mice Marion Duchet-Suchaux,' Pierrette Menanteau,' Herve Le Roux,' Jean-Michel EIsen 2 and Patrick Lechopier' 'Pathologie lnfectieuse et lmmunologie, Institut National de la Recherche Agronomique, Centre de Tours, 37380 Nouzilly, and 2 Station d'Amelioration Genetique des Animaux, Institut National de la Recherche Agronomique, Auzeville, 31326 Castanet-Tolosan, France (Received March 10, 1992; accepted April 4, 1992)
Duchet-Suchaux, M . (Pathologie lnfectieuse et Immunologie, Institut National de la Recherche Agronomique, Centre de Tours, 37380 Nouzilly, France), P . Menanteau, H . Le Roux, J .-M . Elsen and P . Lechopier . Genetic control of resistance to enterotoxigenic Escherichia toll in infant mice . Microbial Pathogenesis 1992 ; 13 : 157-160 . DBA/2 and CBA infant mice orally challenged with bovine enterotoxigenic Escherichia co/i (ETEC) strain B80 presented resistance and susceptibility respectively, as measured by mortality rates 6 days after inoculation . Serum antibodies agglutinating ETEC strain B80 had very low titers in both mouse strains . Mendelian analysis of resistance on F1 and on segregating backcrosses showed that resistance is genetic and dominant . Dominance may be explained either by a mixed control with an overdominant major gene or by a polygenic control with a large heterosis effect. Key words : genetics ; resistance; susceptibility ; enterotoxigenic Escherichia co/i; mouse .
Introduction Diarrhoea in neonate animals is often due to enterotoxigenic Escherichia coil (ETEC) bearing colonization factors and secreting enterotoxins . Genetic resistance of animals to ETEC was firstly described in pigs challenged with ETEC bearing K88 colonization factor, on the basis of an in vitro adherence test .' ,' Monogenic 3 and then multigenic ° control of this resistance has been demonstrated, with dominance of adherence over non-adherence . However, every mechanism of resistance has not yet been elucidated . We developed an infant mouse model of ETEC diarrhoea' which has already been used in virulence," vaccination 8.9 and therapeutics 10 studies . Mortality rates 6 days after inoculation with ETEC strain were used to define susceptibility and resistance of infant mice . Recently, we observed that susceptibility of infant mice depended on ETEC strain and on mouse line ." For instance, some mouse inbred lines (DBA/2, BALB/cBy, C57BL/6) were resistant to bovine ETEC strain B80, which bears K99 colonization factor and secretes heat-stable enterotoxin ." In contrast, CBA and OF1 infant mice were very susceptible to the same ETEC strain ." The aim of this study was to determine whether the control of the resistance is genetic or not . 0882-4010/92/080157+04$08 .00/0
© 1992 Academic Press Limited
1 58
M . Duchet-Suchaux et al .
Results DBA/2 infant mice were resistant to challenge with ETEC strain B80, whereas CBA mice were highly susceptible (Table 1) . These results confirmed those obtained previously ." We observed that F1 (DBA/2xCBA) and F1 (CBAx DBA/2) infant mice presented low mortality rates, close to those of DBA/2 infant mice, 6 days after inoculation with ETEC strain B80 (Table 1) . These results were reproducible in another experiment (data not shown) . Thus, resistance of DBA/2 infant mice to ETEC strain B80 was transmissible in a dominant fashion . Since mortality rates of F1(DBA/2 x CBA) and F1 (CBAx DBA/2) were not statistically different, we used later only one type of F1, DBA/2xCBA, for parental back-crosses, as in this mating female DBA/2 mice are much more prolific than CBA mice . In addition, CBA female mice have a high rate of fetal resorption when mated with DBA/2 males ." In infant mice which were backcrosses of F1 with resistant parental mouse strain DBA/2, ETEC strain B80 induced levels of mortality as low as in DBA/2 or in F1 infant mice, whatever the form of mating (Table 1, experiment 2) . Back-crosses of F1 with susceptible parental mouse strain CBA showed again some susceptibility to ETEC strain B80 . Mortality rates were always lower than 50% and they significantly (P < 0 .01) differed according to the form of mating (Table 1, experiments 2 and 3) . This result could be reproduced in three independent experiments (Table 1 ; data not shown) . The data have been analysed using -she maximum likelihood methods as described by Elston 13 and assuming that the mortality is controlled by an underlying continuous normally distributed variable, the liability, as defined by Falconer ." Different genetic hypotheses were considered, combining the type of inheritance (polygenic, monogenic or mixed), the type of gene (dominant or free) and the presence or not of a maternal effect . From this comparison, which in any case shows a large line effect, first we concluded that the hypothesis for a dominant major gene could not be retained and that the models including a maternal effect fitted the data in a better way in each case . Secondly, we found that the dominant transmission of the resistance may be explained either by a mixed control with an overdominant gene, showing no difference between Table 1 Susceptibility of DBA/2, CBA and derived mouse lines to oral challenge with ETEC strain B80 Experiment Infant mice
1
2
3
Pooled results
Lines DBA/2 CBA
4/30(13) . . . . 33/36 (92)""
0/9(0) . . . 18/26(69) . . .
0/41 (0)"' 14/19(74) """
4/80(5) ""' 65/81 (80)"'
Crosses F1 (DBA/2xCBA) F1 (CBA x D BA/2)
0/91 (0) 2/101 (2)
1/42(2) ND
DBA/2 Back-crosses F1(DBA/2xCBA) x DBA/2 DBA/2x F1 (DBA/2xCBA)
ND ND
2/154 (1) 1/81 (1)
CBA Back-crosses F1 (DBA/2 x CBA) x CBA CBAxF1(DBA/2xCBA)
ND ND
7/58(12) 27/102 (26)'
0/45(0) ND ND ND 9/100(9) . . . 40/125 (32)'"
1/178 (1) b 2/101 (2) b 2/154 (1)b 1/81 (1)b 16/158(10) ""' 67/227 (30)'""
'Dead/inoculated (%) . Differences between both F1 and between both back-crosses were not significant . 'Difference between both back-crosses with CBA was significant (P < 0 .05) . - Differences between DBA/2 and CBA mice and between both back-crosses with CBA were very highly significant (P < 0 .001) . ND : not done. b
Genetic control of resistance
to ETEC
159
the homozygotes but a heterozygote increasing the liability up to 50 per cent of the mean parental deviation, or by a polygenic control with a large heterosis effect (80 per cent of the deviation between the parental liability means) . This second hypothesis could indicate that a limited number of large genes are controlling the resistance . The determination of the number of genes implied in the resistance control would need observations in further generations .
Discussion In the infant mouse model, we observed that resistance to ETEC strain B80 was genetic in origin . Genetic determinism was probably multigenic or mediated by one overdominant gene of resistance . Previous studies in pigs infected with K88 ETEC strain showed that susceptibility was dominant on resistance .` We observed the opposite in mice may be due to species specificity of ETEC in piglets, but not in infant mice . Previous studies have shown that host genotype is important in resistance of mice to a variety of infectious agents, with dominance of resistance ." 7 However, resistance of infant mice to ETEC strain B80 was not controlled by the same genes . For instance, ltys mice 18 such as BALB/cBy and C57BL/6 mice were resistant to challenge with ETEC strain B80, 9 whereas lty' mice like CBA mice were highly susceptible . Thus, Salmonella susceptibility gene Ity does not appear to be important in ETEC resistance of mice . The role of locus H-2 is being now studied by challenge of congenic infant mice with ETEC strain B80 . The infant mouse model affords a new tool for research in genetic determinism of resistance to colibacillosis .
Materials and methods ETEC strain B80 is a bovine strain and was supplied as described previously ."' Inbred mouse lines DBA/2 and CBA were provided, raised and mated as described previously ." Infant mice F1(DBA/2xCBA), F1(CBAxDBA/2), and infant mice which were parental back-crosses F1 (DBA/2 x CBA) x DBA/2, DBA/2 x F1 (DBA/2 x CBA), F1 (DBA/2 x CBA) x CBA and CBA x F1 (DBA/2xCBA) were obtained by ourselves . All lines and crosses between them were raised in similar conditions . All lines were devoid of specific agglutinating antibodies . Oral inoculation of infant mice with ETEC strain B80 was done as described previously ." Briefly the bacterial strain was cultured on slope of trypticase soy agar (BioM6rieux, Marcy I'Etoile, Charbonnieres-les-bains, France) overnight at 37°C, and cells were harvested in phosphate-buffered saline, pH 6 .8 . Suckling infant mice received orally, at 1 day of age, 10 5 bacteria with a calibrated platinum loop . Infected animals were observed daily for 6 days after inoculation and the mortality was recorded . When necessary, mortality rates of infant mice were compared by the chi-square test . As previously,' we excluded from analysis litters in which death occurred within 24 h after inoculation .
This work was partly supported by grant 4835 'Genetique de I'hSte et resistance aux maladies infectieuses et parasitaires' from the Institut National de la Recherche Agronomique . We thank E . Rabouan and N . Sommerhalter for excellent animal care . We are grateful to F . Lantier and P . Le Roy for helpful discussions . We thank F . Lantier for helpful suggestions in the preparation of the manuscript .
References 1. 2.
Rutter JM, Burrows HR, Sellwood R, Gibbons RA. A genetic basis for resistance to enteric disease caused by E. coli. Nature 1975 ; 257 : 135-6 . . Sellwood R, Gibbons RA, Jones GW, Rutter JM . Adhesion of enteropathogenic Escherichia coil to pig intestinal brush borders : the existence of two pig phenotypes . J Med Microbiol 1975 ; 8 : 405-11 .
160
M . Duchet-Suchaux et al .
3 . Gibbons RA, Sellwood R, Burrows M, Hunter PA . Inheritance of resistance to neonatal E. coli diarrhoea in the pig : examination of the genetic system . Theor Appl Genet 1977 ; 51 : 65-70 . 4 . Bijlsma IGW, Bouw J . Inheritance of K88-mediated adhesion of Escherichia coli to jejunal brush borders in pigs : a genetic analysis . Vet Res Commun 1987 ; 11 : 509-18 . 5 . Duchet-Suchaux M . Infant mouse model of E. co/i diarrhoea . Ann Microbiol (Inst Pasteur) 1980 ; 131 B : 239-50 . 6 . Benin A. Virulence factors of enterotoxigenic E. co/i studied in the infant mouse model . Ann Rech Vet 1983 ; 14 : 169-82 . 7 . Bertin A . F41 antigen as a virulence factor in the infant mouse model of Escherichia co/i diarrhoea . J Gen Microbiol 1985 ; 131 : 3037-45 . 8 . Duchet-Suchaux M . Infant mouse model of E. co/i diarrhoea : clinical protection induced by vaccination of the mothers . Ann Rech Vet 1983 ; 14 : 319-31 . 9 . Duchet-Suchaux M . Protective antigens against enterotoxigenic Escherichia coli 0101 : K99, F41 in the infant mouse diarrhea model . Infect Immun 1988 ; 56 : 1364-70 . 10 . Bertin A . Chlorpromazine and propranolol extend survival of infant mice inoculated with enterotoxigenic Escherichia coli. Ann Rech Vet 1981 ; 12 : 137-41 . 11 . Duchet-Suchaux M, Le Maitre C, Bertin A . Differences in susceptibility of inbred and outbred infant mice to enterotoxigenic Escherichia coli of bovine, porcine and human origin . J Med Microbiol 1990 ; 31 : 185-90 . 12 . Chaouat G, Kolb JP, Niger N, Stanislawski M, Wegmann TG . Immunologic consequences of vaccination against abortion in mice . J Immunol 1985 ; 134:1594-8 . 13 . Elston RC . The genetic analysis of quantitative trait differences between two homozygous lines . Genetics 1984 ; 108 : 733-44. 14 . Falconer DS . The inheritance of liability to certain diseases, estimated from the incidence among relatives . Ann Hum Genet 1965 ; 29 : 51 . 15 . O'Brien AD, Rosenstreich DL, Taylor BA . Control of natural resistance to Salmonella typhimurium and Leishmania donovani in mice by closely linked but distinct genetic loci . Nature 1980 ; 287 : 440-2 . 16 . Plant J, Glynn AA . Genetics of resistance to infection with Salmonella typhimurium in mice . J Infect Dis 1976 ; 133 : 72-8 . 17 . Cheers C, McKenzie IFC . Resistance and susceptibility of mice to bacterial infection : genetics of listeriosis . Infect Immun 1978; 19 : 755-62 . 18 . Plant J, Glynn AA. Locating Salmonella resistance gene on mouse chromosome 1 . Clin Exp Immunol 1979 ; 37 : 1-6 .
Short communication Genetic control of resistance to enterotoxigenic Escherichia co/i in infant mice Marion Duchet-Suchaux,' Pierrette Menanteau,' Herve Le Roux,' Jean-Michel EIsen 2 and Patrick Lechopier' 'Pathologie lnfectieuse et lmmunologie, Institut National de la Recherche Agronomique, Centre de Tours, 37380 Nouzilly, and 2 Station d'Amelioration Genetique des Animaux, Institut National de la Recherche Agronomique, Auzeville, 31326 Castanet-Tolosan, France (Received March 10, 1992; accepted April 4, 1992)
Duchet-Suchaux, M . (Pathologie lnfectieuse et Immunologie, Institut National de la Recherche Agronomique, Centre de Tours, 37380 Nouzilly, France), P . Menanteau, H . Le Roux, J .-M . Elsen and P . Lechopier . Genetic control of resistance to enterotoxigenic Escherichia toll in infant mice . Microbial Pathogenesis 1992 ; 13 : 157-160 . DBA/2 and CBA infant mice orally challenged with bovine enterotoxigenic Escherichia co/i (ETEC) strain B80 presented resistance and susceptibility respectively, as measured by mortality rates 6 days after inoculation . Serum antibodies agglutinating ETEC strain B80 had very low titers in both mouse strains . Mendelian analysis of resistance on F1 and on segregating backcrosses showed that resistance is genetic and dominant . Dominance may be explained either by a mixed control with an overdominant major gene or by a polygenic control with a large heterosis effect. Key words : genetics ; resistance; susceptibility ; enterotoxigenic Escherichia co/i; mouse .
Introduction Diarrhoea in neonate animals is often due to enterotoxigenic Escherichia coil (ETEC) bearing colonization factors and secreting enterotoxins . Genetic resistance of animals to ETEC was firstly described in pigs challenged with ETEC bearing K88 colonization factor, on the basis of an in vitro adherence test .' ,' Monogenic 3 and then multigenic ° control of this resistance has been demonstrated, with dominance of adherence over non-adherence . However, every mechanism of resistance has not yet been elucidated . We developed an infant mouse model of ETEC diarrhoea' which has already been used in virulence," vaccination 8.9 and therapeutics 10 studies . Mortality rates 6 days after inoculation with ETEC strain were used to define susceptibility and resistance of infant mice . Recently, we observed that susceptibility of infant mice depended on ETEC strain and on mouse line ." For instance, some mouse inbred lines (DBA/2, BALB/cBy, C57BL/6) were resistant to bovine ETEC strain B80, which bears K99 colonization factor and secretes heat-stable enterotoxin ." In contrast, CBA and OF1 infant mice were very susceptible to the same ETEC strain ." The aim of this study was to determine whether the control of the resistance is genetic or not . 0882-4010/92/080157+04$08 .00/0
© 1992 Academic Press Limited
1 58
M . Duchet-Suchaux et al .
Results DBA/2 infant mice were resistant to challenge with ETEC strain B80, whereas CBA mice were highly susceptible (Table 1) . These results confirmed those obtained previously ." We observed that F1 (DBA/2xCBA) and F1 (CBAx DBA/2) infant mice presented low mortality rates, close to those of DBA/2 infant mice, 6 days after inoculation with ETEC strain B80 (Table 1) . These results were reproducible in another experiment (data not shown) . Thus, resistance of DBA/2 infant mice to ETEC strain B80 was transmissible in a dominant fashion . Since mortality rates of F1(DBA/2 x CBA) and F1 (CBAx DBA/2) were not statistically different, we used later only one type of F1, DBA/2xCBA, for parental back-crosses, as in this mating female DBA/2 mice are much more prolific than CBA mice . In addition, CBA female mice have a high rate of fetal resorption when mated with DBA/2 males ." In infant mice which were backcrosses of F1 with resistant parental mouse strain DBA/2, ETEC strain B80 induced levels of mortality as low as in DBA/2 or in F1 infant mice, whatever the form of mating (Table 1, experiment 2) . Back-crosses of F1 with susceptible parental mouse strain CBA showed again some susceptibility to ETEC strain B80 . Mortality rates were always lower than 50% and they significantly (P < 0 .01) differed according to the form of mating (Table 1, experiments 2 and 3) . This result could be reproduced in three independent experiments (Table 1 ; data not shown) . The data have been analysed using -she maximum likelihood methods as described by Elston 13 and assuming that the mortality is controlled by an underlying continuous normally distributed variable, the liability, as defined by Falconer ." Different genetic hypotheses were considered, combining the type of inheritance (polygenic, monogenic or mixed), the type of gene (dominant or free) and the presence or not of a maternal effect . From this comparison, which in any case shows a large line effect, first we concluded that the hypothesis for a dominant major gene could not be retained and that the models including a maternal effect fitted the data in a better way in each case . Secondly, we found that the dominant transmission of the resistance may be explained either by a mixed control with an overdominant gene, showing no difference between Table 1 Susceptibility of DBA/2, CBA and derived mouse lines to oral challenge with ETEC strain B80 Experiment Infant mice
1
2
3
Pooled results
Lines DBA/2 CBA
4/30(13) . . . . 33/36 (92)""
0/9(0) . . . 18/26(69) . . .
0/41 (0)"' 14/19(74) """
4/80(5) ""' 65/81 (80)"'
Crosses F1 (DBA/2xCBA) F1 (CBA x D BA/2)
0/91 (0) 2/101 (2)
1/42(2) ND
DBA/2 Back-crosses F1(DBA/2xCBA) x DBA/2 DBA/2x F1 (DBA/2xCBA)
ND ND
2/154 (1) 1/81 (1)
CBA Back-crosses F1 (DBA/2 x CBA) x CBA CBAxF1(DBA/2xCBA)
ND ND
7/58(12) 27/102 (26)'
0/45(0) ND ND ND 9/100(9) . . . 40/125 (32)'"
1/178 (1) b 2/101 (2) b 2/154 (1)b 1/81 (1)b 16/158(10) ""' 67/227 (30)'""
'Dead/inoculated (%) . Differences between both F1 and between both back-crosses were not significant . 'Difference between both back-crosses with CBA was significant (P < 0 .05) . - Differences between DBA/2 and CBA mice and between both back-crosses with CBA were very highly significant (P < 0 .001) . ND : not done. b
Genetic control of resistance
to ETEC
159
the homozygotes but a heterozygote increasing the liability up to 50 per cent of the mean parental deviation, or by a polygenic control with a large heterosis effect (80 per cent of the deviation between the parental liability means) . This second hypothesis could indicate that a limited number of large genes are controlling the resistance . The determination of the number of genes implied in the resistance control would need observations in further generations .
Discussion In the infant mouse model, we observed that resistance to ETEC strain B80 was genetic in origin . Genetic determinism was probably multigenic or mediated by one overdominant gene of resistance . Previous studies in pigs infected with K88 ETEC strain showed that susceptibility was dominant on resistance .` We observed the opposite in mice may be due to species specificity of ETEC in piglets, but not in infant mice . Previous studies have shown that host genotype is important in resistance of mice to a variety of infectious agents, with dominance of resistance ." 7 However, resistance of infant mice to ETEC strain B80 was not controlled by the same genes . For instance, ltys mice 18 such as BALB/cBy and C57BL/6 mice were resistant to challenge with ETEC strain B80, 9 whereas lty' mice like CBA mice were highly susceptible . Thus, Salmonella susceptibility gene Ity does not appear to be important in ETEC resistance of mice . The role of locus H-2 is being now studied by challenge of congenic infant mice with ETEC strain B80 . The infant mouse model affords a new tool for research in genetic determinism of resistance to colibacillosis .
Materials and methods ETEC strain B80 is a bovine strain and was supplied as described previously ."' Inbred mouse lines DBA/2 and CBA were provided, raised and mated as described previously ." Infant mice F1(DBA/2xCBA), F1(CBAxDBA/2), and infant mice which were parental back-crosses F1 (DBA/2 x CBA) x DBA/2, DBA/2 x F1 (DBA/2 x CBA), F1 (DBA/2 x CBA) x CBA and CBA x F1 (DBA/2xCBA) were obtained by ourselves . All lines and crosses between them were raised in similar conditions . All lines were devoid of specific agglutinating antibodies . Oral inoculation of infant mice with ETEC strain B80 was done as described previously ." Briefly the bacterial strain was cultured on slope of trypticase soy agar (BioM6rieux, Marcy I'Etoile, Charbonnieres-les-bains, France) overnight at 37°C, and cells were harvested in phosphate-buffered saline, pH 6 .8 . Suckling infant mice received orally, at 1 day of age, 10 5 bacteria with a calibrated platinum loop . Infected animals were observed daily for 6 days after inoculation and the mortality was recorded . When necessary, mortality rates of infant mice were compared by the chi-square test . As previously,' we excluded from analysis litters in which death occurred within 24 h after inoculation .
This work was partly supported by grant 4835 'Genetique de I'hSte et resistance aux maladies infectieuses et parasitaires' from the Institut National de la Recherche Agronomique . We thank E . Rabouan and N . Sommerhalter for excellent animal care . We are grateful to F . Lantier and P . Le Roy for helpful discussions . We thank F . Lantier for helpful suggestions in the preparation of the manuscript .
References 1. 2.
Rutter JM, Burrows HR, Sellwood R, Gibbons RA. A genetic basis for resistance to enteric disease caused by E. coli. Nature 1975 ; 257 : 135-6 . . Sellwood R, Gibbons RA, Jones GW, Rutter JM . Adhesion of enteropathogenic Escherichia coil to pig intestinal brush borders : the existence of two pig phenotypes . J Med Microbiol 1975 ; 8 : 405-11 .
160
M . Duchet-Suchaux et al .
3 . Gibbons RA, Sellwood R, Burrows M, Hunter PA . Inheritance of resistance to neonatal E. coli diarrhoea in the pig : examination of the genetic system . Theor Appl Genet 1977 ; 51 : 65-70 . 4 . Bijlsma IGW, Bouw J . Inheritance of K88-mediated adhesion of Escherichia coli to jejunal brush borders in pigs : a genetic analysis . Vet Res Commun 1987 ; 11 : 509-18 . 5 . Duchet-Suchaux M . Infant mouse model of E. co/i diarrhoea . Ann Microbiol (Inst Pasteur) 1980 ; 131 B : 239-50 . 6 . Benin A. Virulence factors of enterotoxigenic E. co/i studied in the infant mouse model . Ann Rech Vet 1983 ; 14 : 169-82 . 7 . Bertin A . F41 antigen as a virulence factor in the infant mouse model of Escherichia co/i diarrhoea . J Gen Microbiol 1985 ; 131 : 3037-45 . 8 . Duchet-Suchaux M . Infant mouse model of E. co/i diarrhoea : clinical protection induced by vaccination of the mothers . Ann Rech Vet 1983 ; 14 : 319-31 . 9 . Duchet-Suchaux M . Protective antigens against enterotoxigenic Escherichia coli 0101 : K99, F41 in the infant mouse diarrhea model . Infect Immun 1988 ; 56 : 1364-70 . 10 . Bertin A . Chlorpromazine and propranolol extend survival of infant mice inoculated with enterotoxigenic Escherichia coli. Ann Rech Vet 1981 ; 12 : 137-41 . 11 . Duchet-Suchaux M, Le Maitre C, Bertin A . Differences in susceptibility of inbred and outbred infant mice to enterotoxigenic Escherichia coli of bovine, porcine and human origin . J Med Microbiol 1990 ; 31 : 185-90 . 12 . Chaouat G, Kolb JP, Niger N, Stanislawski M, Wegmann TG . Immunologic consequences of vaccination against abortion in mice . J Immunol 1985 ; 134:1594-8 . 13 . Elston RC . The genetic analysis of quantitative trait differences between two homozygous lines . Genetics 1984 ; 108 : 733-44. 14 . Falconer DS . The inheritance of liability to certain diseases, estimated from the incidence among relatives . Ann Hum Genet 1965 ; 29 : 51 . 15 . O'Brien AD, Rosenstreich DL, Taylor BA . Control of natural resistance to Salmonella typhimurium and Leishmania donovani in mice by closely linked but distinct genetic loci . Nature 1980 ; 287 : 440-2 . 16 . Plant J, Glynn AA . Genetics of resistance to infection with Salmonella typhimurium in mice . J Infect Dis 1976 ; 133 : 72-8 . 17 . Cheers C, McKenzie IFC . Resistance and susceptibility of mice to bacterial infection : genetics of listeriosis . Infect Immun 1978; 19 : 755-62 . 18 . Plant J, Glynn AA. Locating Salmonella resistance gene on mouse chromosome 1 . Clin Exp Immunol 1979 ; 37 : 1-6 .
