8536d_cho7 161-184 8/16/02 12: 09 PM Page 165 mac100 mac 100: 1?/8_tm: 8536d: Goldsby et al./Immunology Se Major Histocompatibility Complex CHAPTER 7 URE 7-3 Production of congenic mouse Cross AB, which has the genetic background of arental strain a but the H-2 complex of strain B Crossing inbred strain A(H-2)with strain B(H-2) generates Fi progeny that are heterozygous(a/b) at all H-2 loci. The Fi progeny are interbred to pro interbreeding duce an F2 generation, which includes a/a, a/b, and b/b individuals. The F2 progeny homozygous r the B-strain H-2 complex are selected by their ability to reject a skin graft from strain A; any prog from future breeding. The selected b/b homozy Strain-A skin grafts gous mice are then backcrossed to strain A; the re- nd selection for ability reject an A-strain graft is repeated for at least 12 backcross restored at all loci except the H-2 locus, which for the b strain Interbreed. select and Strain a. B except at a single genetic locus or region. Any pheno- typic differences that can be detected between congenic strains are related to the genetic region that distinguishes ABA邱 the strains. Congenic strains that are identical with each Parental other except at the mHc can be produced by a series of crosses, backcrosses, and selections. Figure 7-3 outlines the Congenic B10.A steps by which the H-2 complex of homozygous strain B B10.A(2R) b2 an be introduced into the background genes of homozy- gous strain a to generate a congenic strain, denoted A B B10.A(4R)b4 The first letter in a congenic strain designation refers to the B10.A(18R)i8 strain providing the genetic background and the second letter to the strain providing the genetically different MHC FIGURE 7.4 Examples of recombinant congenic mouse strains region. Thus, strain A.B will be genetically identical to generated during production of the B10. A strain from parental strain 10(H-2)and parental strain A(H-2).Crossover events within the strain A except for the MHC locus or loci contributed by H-2 complex produce recombinant strains, which have a-haplotype strain B During production of congenic mouse strains, a crossover alleles(blue)at some H-2 loci and b-haplotype alleles (orange)at event sometimes occurs within the H-2 complex, yielding a other loci recombinant strain that differs from the parental strains or the congenic strain at one or a few loci within the H-2 duction of a B10. A congenic strain. Such recombinant complex Figure 7-4 depicts haplotypes present in several re- strains have been extremely useful in analyzing the MHC be- binant congenic strains that were obtained during pro- cause they permit comparisons of functional differencesexcept at a single genetic locus or region. Any pheno￾typic differences that can be detected between congenic strains are related to the genetic region that distinguishes the strains. Congenic strains that are identical with each other except at the MHC can be produced by a series of crosses, backcrosses, and selections. Figure 7-3 outlines the steps by which the H-2 complex of homozygous strain B can be introduced into the background genes of homozy￾gous strain A to generate a congenic strain, denoted A.B. The first letter in a congenic strain designation refers to the strain providing the genetic background and the second letter to the strain providing the genetically different MHC region. Thus, strain A.B will be genetically identical to strain A except for the MHC locus or loci contributed by strain B. During production of congenic mouse strains, a crossover event sometimes occurs within the H-2 complex, yielding a recombinant strain that differs from the parental strains or the congenic strain at one or a few loci within the H-2 complex. Figure 7-4 depicts haplotypes present in several re￾combinant congenic strains that were obtained during pro￾duction of a B10.A congenic strain. Such recombinant strains have been extremely useful in analyzing the MHC be￾cause they permit comparisons of functional differences Major Histocompatibility Complex CHAPTER 7 165 F2 a/a b/b × a/b a /b × Strain-A skin grafts Cross Interbreeding Select for b/b at H-2 complex F1 a/a a/b a/b b/b Strain A × a/b a/b × Backcross Interbreed, select, and backcross for ≤ 10 cycles ≤ Strain A•B a/a FIGURE 7-3 Production of congenic mouse strain A.B, which has the genetic background of parental strain A but the H-2 complex of strain B. Crossing inbred strain A (H-2a ) with strain B (H-2b ) generates F1 progeny that are heterozygous (a/b) at all H-2 loci. The F1 progeny are interbred to pro￾duce an F2 generation, which includes a/a, a/b, and b/b individuals. The F2 progeny homozygous for the B-strain H-2 complex are selected by their ability to reject a skin graft from strain A; any prog￾eny that accept an A-strain graft are eliminated from future breeding. The selected b/b homozy￾gous mice are then backcrossed to strain A; the re￾sulting progeny are again interbred and their offspring are again selected for b/b homozygosity at the H-2 complex. This process of backcrossing to strain A, intercrossing, and selection for ability to reject an A-strain graft is repeated for at least 12 generations. In this way A-strain homozygosity is restored at all loci except the H-2 locus, which is homozygous for the B strain. Strain Parental Congenic Recombinant congenic A B10 B10.A B10.A (3R) B10.A (2R) B10.A (4R) B10.A (18R) H-2 haplotype a b a i3 h2 h4 i18 KA A E E S D H-2 loci β β α α FIGURE 7-4 Examples of recombinant congenic mouse strains generated during production of the B10.A strain from parental strain B10 (H-2b ) and parental strain A (H-2a ). Crossover events within the H-2 complex produce recombinant strains, which have a-haplotype alleles (blue) at some H-2 loci and b-haplotype alleles (orange) at other loci. 8536d_ch07_161-184 8/16/02 12:09 PM Page 165 mac100 mac 100: 1268_tm:8536d:Goldsby et al. / Immunology 5e-: