Abstract. After skeletal muscle is denervated, fibroblasts near neuromuscular junctions proliferate more than fibroblasts distant from synaptic sites, and they accumulate adhesive molecules such as tenascin (Gatchalian, C. L., M. Schachner, and J. R. Sanes. 1989. J. Cell Biol. 108:1873-1890. This response could reflect signals that arise perisynaptically after denervation, preexisting differences between perisynaptic and extrasynaptic fibroblasts, or both. Here, we describe a line of transgenic mice in which patterns of transgene expression provide direct evidence for differences between perisynaptic and extrasynaptic fibroblasts in norreal muscle.Transgenic mice were generated using regulatory elements from a major histocompatibility complex (MHC) class I gene linked to the Escherichia coli/~-galactosidase (lacZ) gene. Expression of lacZ was detected histochemically. In each of eight lines, lacZ was detected in different subsets of cells, none of which included lymphocytes. In contrast, endogeous MHC is expressed in most tissues and at high levels in lymphocytes. Thus, the MHC gene sequences appeared inactive in the transgene, and lacZ expression was apparently controlled by genomic regulatory elements that were specific for the insertion site.In one line, cells close to the neuromuscular junction were lacZ positive in embryonic and young postnatal mice. Electron microscopy identified these cells as fibroblasts and Schwann cells associated with motor nerve terminals, as well as endoneurial fibroblasts, perineurial cells, and Schwann cells in the distal branches of motor nerves. No intramuscular cells >200 #m from synaptic sites were lacZ positive. These result indicate that there are molecular differences between perisynaptic and extrasynaptic fibroblasts even in normal muscle and that diverse perisynaptic cell types share a specific pattern of gene expression.

Transgenic mice expressing HLA-DQA1*0301 and HLA-DQB1*0302 genes (DQ8) were produced. The transgenes were then transferred into mouse (Ab degrees) class II negative mice: the only class II molecules expressed in these animals were therefore coded by the HLA-DQ8 genes. Good expression of HLA-DQ molecules was found. Both CD4+ T cells and DQ8-specific T-cell receptor V beta expressing cells were positively selected in these mice. The HLA-DQ8 molecules expressed in these animals can present various foreign and self antigens and induce T-cell proliferation in vitro. These mice will be invaluable in future studies of the structure and function of HLA-DQ8 genes.

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One hundred and twelve South Indian males with non-diabetic peripheral vascular disease of the lower limb were classified clinically into three groups according to the level of obstruction (aorto-iliac, 26 patients; femoropopliteal, 46 patients; distal, 40 patients). Arteriography was done in 65 patients and serum lipid estimations in 69. In the aorto-iliac group the mean age was 45 years (+/- 11.6 s.d.); 23 per cent had hypertension, 28 per cent polycythaemia and 55 per cent hyperlipidaemia. Aortography suggested atheroma in most. In the femoropopliteal group the mean age was 39 years (+/- 12.8); 22 per cent had hypertension, 11 per cent polycythaemia and 21 per cent hyperlipidaemia. Arteriography showed lesions typical of atheroma in many and was consistent with thrombo-angiitis obliterans in some. In the distal group the mean age was 37 years (+/- 9.8); 8 per cent had hypertension, 20 per cent polycythaemia, 25 per cent hyperlipidaemia and 20 per cent had distal arterial disease of the upper limb. Arteriography was consistent with thrombo-angiitis obliterans in most cases. Atheroma seemed to be implicated in 96 per cent of the aorto-iliac group and in 64 per cent of the femoropopliteal group.

Recombinant mouse strains with crossovers within the H-2 complex have been extremely important in the development of the current genetic map of this important gene complex. By using recombinant mouse strains, the I region of the H-2 complex was originally divided into five subregions: I-A, I-B, I-J, I-E, and I-C (1). Recent molecular genetic analysis (2, 3) has shown that the I region spans a 230 kb stretch of DNA, consisting of six class II genes: Ate2, A s, A~, Ee, E~2, and E~. A~ and A~ genes code the two polypeptide chains that form the I-A molecule, while Ee and E~ genes code the two polypeptide chains that form the I-E molecule. AO2 and Ee~ genes have been shown to produce mRNA, but it is not known whether this mRNA is translated into functional polypeptides (4-6).To relate the molecular map with the genetic map, Steinmetz et al. (2) and Kobori et al. (7) analyzed six intra-I region recombinants and showed that, in all cases, the crossover point occurred in a 4 kb DNA segment within the Ee gene. These results were surprising in two respects. First, it suggested that the I-B and I-J subregions that were defined genetically according to functional and serological phenotype do not encode classical la gene products, and therefore the immunological phenomena previously mapped to these subregions must be accounted for by other means. Second, it suggested that recombination within the MHC may not be random, but is localized to specific sites termed recombinational hot spots.Over the last few years our laboratory has produced additional recombinant mouse strains with crossovers in the H-2 complex. We have recently begun a major effort to determine the crossover points in these recombinants at the DNA level. In this paper we report on the DNA restriction fragment analysis of nine recombinant mouse strains that, by serological analysis, contain crossover points in the I region. Seven of these recombinant mouse strains have crossover points in the I-E subregion within an -12-14 kb segment of DNA, which contains the E~ gene. This analysis shows that a second recombinational hot spot exists in the I-E subregion.