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J A Martignetti A A Aqeel W A Sewairi C E Boumah M Kambouris S A Mayouf K V Sheth W A Eid O Dowling J Harris M J Glucksman S Bahabri B F Meyer R J Desnick 《Nature genetics》2001,28(3):261-265
The inherited osteolyses or 'vanishing bone' syndromes are a group of rare disorders of unknown etiology characterized by destruction and resorption of affected bones. The multicentric osteolyses are notable for interphalangeal joint erosions that mimic severe juvenile rheumatoid arthritis (OMIMs 166300, 259600, 259610 and 277950). We recently described an autosomal recessive form of multicentric osteolysis with carpal and tarsal resorption, crippling arthritic changes, marked osteoporosis, palmar and plantar subcutaneous nodules and distinctive facies in a number of consanguineous Saudi Arabian families. We localized the disease gene to 16q12-21 by using members of these families for a genome-wide search for homozygous-by-descent microsatellite markers. Haplotype analysis narrowed the critical region to a 1.2-cM region that spans the gene encoding MMP-2 (gelatinase A, collagenase type IV; (ref. 3). We detected no MMP2 enzymatic activity in the serum or fibroblasts of affected family members. We identified two family-specific homoallelic MMP2 mutations: R101H and Y244X. The nonsense mutation effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains. Based on molecular modeling, the missense mutation disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion. 相似文献
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Induction of hemopoietic chimerism in the caprine fetus by intraperitoneal injection of fetal liver cells 总被引:1,自引:0,他引:1
R. D. Pearce D. Kiehm D. T. Armstrong P. B. Little J. W. Callahan L. R. Klunder J. T. R. Clarke 《Cellular and molecular life sciences : CMLS》1989,45(3):307-308
Summary Intraperitoneal injection of allogeneic liver cells from 43-day-old male fetuses into normal 60-day female goat fetuses resulted in persistent hemopoietic chimerism in surviving recipients without clinical evidence of graft-versus-host disease. Transplantation of normal fetal liver cells into preimmunocompetent goat fetuses affected with -D-mannosidosis may provide an alternative strategy for evaluating hemopoietic stem cell transplantation in the treatment of human lysosomal storage diseases. 相似文献
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H. -P. Lipp H. Schwegler W. E. Crusio D. P. Wolfer M. -C. Leisinger-Trigona B. Heimrich P. Driscoll 《Cellular and molecular life sciences : CMLS》1989,45(9):845-859
Summary Genetically-defined rodent strains permit the identification of hippocampal traits which are of functional relevance for the performance of two-way avoidance behavior. This is exemplified here by analyzing the relationship between infrapyramidal mossy fibers (a tiny projection terminating upon the basal dendrites of hippocampal pyramidal neurons) and two-way avoidance learning in about 800 animals. The necessary steps include 1) identification of structural traits sensitive to selective breeding for extremes in two-way avoidance, 2) testing the robustness of the associations found by studying individual and genetical correlations between hippocampal traits and behavior, 3) establishing causal relationships by Mendelian crossing of strains with extreme structural traits and studying the behavioral consequences of such structural randomization, 4) confirming causal relationships by manipulating the structural variable in inbred (isogenic) strains, thereby eliminating the possibility of genetic linkage, and 5) ruling out the possibility of spurious associations by studying the correlations between the hippocampal trait and other behaviors known to depend on hippocampal functioning.In comparison with the classical lesion approach for identifying relationships between brain and behavior, the present procedure appears to be superior in two aspects: it is non-invasive, and it focuses automatically on those brain traits which are used by natural selection to shape behaviorally-defined animal populations, i.e., it reveals the natural regulators of behavior. 相似文献
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Summary Monarch butterflies sequester cardenolides from their larval host plants in the milkweed genusAsclepias for use in defense against predation. Of 108Asclepias species in North America, monarchs are known to feed as larvae on 27. Research on 11 of these has shown that monarchs sequester cardenolides most effectively, to an asymptote of approximately 350 g/0.1 g dry butterfly, from plants with intermediate cardenolide contents rather than from those with very high or very low cardenolide contents. SinceAsclepias host plant species are distributed widely in space and time across the continent, monarchs exploit them by migration between breeding and overwintering areas. After overwintering in central Mexico, spring migrants east of the Rocky Mountains exploit three predominantAsclepias species in the southern USA that have moderately high cardenolide contents. Monarchs sequester cardenolides very effectively from these species. First generation butterflies are thus well protected against predators and continue the migration north. Across the northern USA and southern Canada most summer breeding occurs on a fourthAsclepias species and in autumn most of these monarchs migrate back to Mexican overwintering sites. The ecological implications of this cycle of cardenolide sequestration for the evolution of monarch migration are discussed. 相似文献