Kirsten Fischer Lindahl

Gene organization and recombinational hotspots in the murine major histocompatibility complex

By chromosome walking in the major histocompatibility complex (MHC) of the BALB/c mouse, we have linked the K region to the I region at the molecular level. Forty-nine overlapping cosmid clones define a stretch of about 600 kb of DNA containing 2 class I and 7 class II genes. Eleven independent recombination events were mapped between the K and the I region marker loci by Southern blot analysis of polymorphic restriction sites. Eight of these events involved crossing-over, at an unusually high frequency of 0.6%-1.5% between genes from Mus musculus castaneus and laboratory mouse strains, and they were confined to two small stretches of DNA. We conclude that recombination hotspots are present at these positions in the two M.m. castaneus MHC haplotypes tested. In contrast, several MHC haplotypes of laboratory mice appear to lack those hotspots.

Hotspots of homologous recombination in mammalian genomes

Abstract The mouse major histocompatibility complex (MHC) offers a unique opportunity for investigating whether homologous meiotic recombination happens at random or at specific sites. Many recombinants have been characterized and saved because of their usefulness in immunological research, and the molecular cloning of the MHC has made it possible to map the crossover points molecularly. Confinement of most of the crossover points to small regions of DNA indicates the specific sequences are involved in homologous meiotic recombination.

Beta-2 microglobulin types in mice of wild origin

To determine the distribution of beta-2 microglobulin (B2m) alleles in wild mice we have typed mice derived from natural populations in Europe, North Africa, South America, and East Asia. Mus musculus domesticus mice from Germany, France, Italy, and Peru were all B2maas were most from the United Kingdom. M.m. musculus mice from Denmark and Czechoslovakia, several stocks of M.m. molossinus from Japan, and M.m. castaneus from China, Thailand, and the Philippines were of B2mbtype. This is consistent with the notion that C57BL/6 may have obtained some of its genes, including B2m, from Eastern mice. A BgII restriction site characteristic of B2mbwas also found in mice from Czechoslovakia and Japan, confirming that B2mbis a naturally occurring allele of B2m. A new type of β2m (β2mw1) was found in four stocks of M. spretus from Portugal, Spain, and Morocco. This molecule differs in apparent size and charge from the a and b types. β2mw2 was found together with β2 ma in one stock of M.m. domesticus (brevirostris) from Morocco. β2mw3 and β2mw4 were found in a few M. m. bactrianus from Pakistan. In all cases tested, these new β2m molecules associate with class I histocompatibility antigens.

Mitochondrial inheritance in mice

Abstract Mitochondrial DNA is strictly maternally inherited, in mice and in other animals. Six of the 13 proteins it encodes are known to be subunits of mitochondrial enzymes, but the rest can also be demonstrated in tissue sections with antibodies. Despite considerable nucleotide sequence divergence among wild mice, the only known phenotypic variation associated with mitochondrial DNA is a transplantation antigen, Mta. the appearance of Mta on the cell surface is the first indication that proteins may be exported from mitochondria. The mechanism of material inheritance and how mitochondrial homogeneity is maintained are still unknown, as are the nature and function of seven of the mitochondrial proteins and of the cell surface antigen, Mta.

Expression of the I-E target antigen for T-cell killing requires two genes

TheH−2Ik region encodes at least two different target antigens for unrestricted T-cell mediated killing. The first is controlled by theI−A region alone and the second depends on a pair of alleles, one located to the left ofI−B (presumably inI−A) and the other to the right ofI−J (presumably inI−E). Hence, effector cells nominally specific for a product of theI−E region do not kill target cells with the sameI−E region as the stimulator unless theI−A region is also shared. Some effectors specific forH−2Ik, such as A.TH anti-A.TL and B10.A(4R) anti-B10.A(2R), cross-react with B10.A(3R) and B10.A(5R) target cells. A product of theH−2b haplotype was shown to complement products of theH−2d orH−2k haplotypes in forming this cross-reactive determinant. The results are consistent with recent biochemical data on the component chains of Ia antigens.