摘要:

As early as 1936, Penrose noted a 25% excess of males in the population of retarded individuals80. Family studies in which the males were primarily affected indicated a sex-linked defect59, which later proved to be X-linked17,55,76,84. These heterogeneous forms of X-linked mental retardation have now been classified into 3 basic syndromes: (1) Renpenning syndrome, where males are short in stature, have small heads and normal to small testes23,84; (2) Martin-Bell syndrome, where the males have a long face, prominent forehead and ears, enlarged testes (macro-orchidism) and a fragile site near the terminal region of the long arm of the X-chromosome59,87; and (3) non-specific X-linked mental retardation, where the males have neither physical abnormalities nor fragile sites on the X-chromosome39. For a more detailed description of the history and clinical aspects, see reviews42,99100,102.

ISSN:0167-7063    

DOI:10.3109/01677068409107086

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

摘要:

A coupled assay using [14C] 4-aminobutyric acid and a direct assay using [14C]succinic semialdehyde have been designed to assay the activity of succinic semialdehyde dehydrogenase in a patient with 4-hydroxybutyric aciduria and family members. In the coupled assay less than 3% of control succinic semialdehyde dehydrogenase activity was found in lysates of lymphocytes isolated from whole blood of the patient. In the direct assay there was no detectable activity of the enzyme in lysates of isolated lymphocytes or cultured lymphoblasts. Results indicated the parents to be heterozygous carriers of the abnormal gene, consistent with an autosomal recessive inheritance.

ISSN:0167-7063    

DOI:10.3109/01677068409107087

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

摘要:

In vitro culture of central nervous system neurons fromDrosophilalarvae enables direct examination of effects of neurological mutations at a single-cell level not readily amenable to in vivo experimentation. Using this system, we examined the cytotoxic effect of veratridine, which selectively causes persistent activation of sodium channels, on the mutantsparaandnapknown to have a temperature-dependent block in propagation of nerve action potentials. Even at a permissive temperature (22oC) for the mutant flies, the veratridine-induced neuronal lethality was significantly lower in bothparaandnapcultures than in normal cultures. At a temperature (35oC) causing paralysis of mutant flies,napneurons showed the same high degree of resistance to veratridine; whileparaneurons showed an increased resistance to a level similar to that ofnapneurons. A similar reduction in the veratridine-induced neuronal death was also observed in normal cultures that were pretreated with the sodium channel blocker tetrodotoxin. These results support the idea that both para andnapaffect sodium channel functions at the level of isolated single neurons. It was also found thatparaandnapmutations, like the sodium channel blocker tetrodotoxin, do not affect the morphological differentiation and survival of central nervous system neurons in culture. These findings indicate that functional sodium channels are not required for neurite outgrowth and survival of neurons at this developmental stage.

ISSN:0167-7063    

DOI:10.3109/01677068409107088

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

摘要:

These experiments address the mechanism of action of the persistence of proliferation in the cerebellar external granule layer (EGL) by comparing congenital hypothyroidism due to a recessive mutation in mice to thestaggerermouse mutant. In both cases persistence of the EGL can be demonstrated histologically, with the process more drawn out instaggererthan inhypothyroid.This correlates with higher than normal levels of the enzyme thymidine kinase, a biochemical marker of proliferation, in both mutants. It is hypothesized that the proliferation of EGL cells in both cases is controlled by effects of the mutations on the maturation rate of the Purkinje cells, possibly with other cell types as intermediates.

ISSN:0167-7063    

DOI:10.3109/01677068409107089

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

摘要:

In BALB/c mice the lamination of the pyramidal cell layer of area CA3c of the hippocampus is abnormal in that early-generated neurons are superficial and late-generated neurons are deep. To determine the mode of inheritance of this strain difference, the laminar distribution of mossy fibers and hippocampal pyramidal cells was examined using the Timm's sulfide silver method in BALB/c C57BL/6 Fl and F2 hybrids, in BALB/cByJ and C57BL/6J mice which were fostered to females of the other strain before receiving their first meal, and in the CXB series of recombinant inbred strains (originally derived using BALB/c and C57BL/6 as progenitor strains). The pattern of hippocampal lamination was classified as“BALB/c-like”if pyramidal cells were present below an iwrapyramidal mossy fiber layer or as“B6-like”if only aninfra-pyramidal mossy fiber layer was present. In both male and female CB6F1 and B6CF1 hybrids the distribution of mossy fibers is BALB/c-Iike. In 7 of 9 F2 hybrids the distribution was BALB/c-like and in the remaining 2 B6-like. In the cross-fostered mice the pattern was always the same as normally raised mice of the same genotype. Of the recombinant inbred strains, 5 (CXBD, CXBG, CXBH, CXBI, and CXBK) had BALB/c-like hippocampal lamination and 2 (CXBE and CXBJ) had B6-like lamination. These results are consistent with inheritance by means of a single autosomal dominant (or semi-dominant) gene. The provisional name“Hippocampal“lamination defect”and gene symbolHidare suggested. TheHidmutation is only the third known neurological mutation in mice which apparently affects neuronal migration, and the fact that it affects only a single subdivision of the hippocampus indicates thatHidmay be a useful tool for future studies of the development of the central nervous system and particularly of the cell biology of neuronal migration and neuronal specificity.

ISSN:0167-7063    

DOI:10.3109/01677068409107090

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor

摘要:

The analysis of Ca2+-channel function in the single-celled eukaryoteParameciumcan be extended to a biochemical level based on recent observations that transfer of cytoplasm from wild-type cells into mutants lacking Ca2+-channel function (“pawn”mutants) causes the mutant cells to regain Ca2+-channel activity. Using a convenient behavioral assay for Ca2+-channel function, we have used microinjection of cytoplasmic fractions into mutant cells to enrich for and characterize those components from wild-type cytoplasm which can“cure”cells carrying mutations in the 3 different pawn genes affecting Ca2+-channel activity (pwA,pwB, andpwC). In each case, the curing factor appears to be a protein component of an intracellular membrane. They are distinguishable on the basis of thermal, pH and divalent ion sensitivities. In addition, the factor curingIhepwCmutational defect has been purified more than 180-fold. Furthermore, thepwB curing activity appears to be amplified during sequential transfer betweenpwBcells.

ISSN:0167-7063    

DOI:10.3109/01677068409107091

出版商:Taylor&Francis    

年代:1984

数据来源: Taylor