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Influence of paternally imprinted genes on development. 总被引:4,自引:0,他引:4
S C Barton A C Ferguson-Smith R Fundele M A Surani 《Development (Cambridge, England)》1991,113(2):679-687
The parental origin of chromosomes is critical for normal development in the mouse because some genes are imprinted resulting in a predetermined preferential expression of one of the alleles. Duplication of the paternal (AG: androgenones) or maternal (GG/PG: gynogenones/parthenogenones) genomes will result in an excess or deficiency of gene dosage with corresponding phenotypic effects. Here, we report on the effects of paternally imprinted genes on development following introduction of the AG inner cell mass into normal blastocysts. There was a striking increase in embryonic growth by up to 50%, and a characteristic change in embryonic shape, partly because of the corresponding increase in length of the anterior-posterior axis. These changes, between e12-e15, were proportional to the contribution from AG cells to the embryo. However, a contribution of AG cells in excess of 50% was invariably lethal as development progressed to e15. A limited number of chimeras were capable of full-term development provided there was a relatively low contribution from AG cells. The distribution of AG cells in chimeras was not uniform, especially later in development when there was a disproportionate presence of AG cells in the mesodermally derived tissues. Their contribution was consistently greater in the heart and skeletal muscle, but was considerably lower in the brain. Chimeras detected after birth were either dead or developed severe abnormalities of the skeletal elements, particularly of the ribs which were enlarged, distorted and fused, with greatly increased cartilaginous material with an absence of normal ossification. These phenotypic effects in chimeras are reciprocal to those observed in the presence of GG/PG cells, which resulted in a substantial size reduction approaching 50%.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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J S Barton D L Vandivort D H Heacock J A Coffman K A Trygg 《The Biochemical journal》1987,247(3):505-511
The assembly kinetics of microtubule protein are altered by ionic strength, temperature and Mg2+, but not by pH. High ionic strength (I0.2), low temperature (T less than 30 degrees C) and elevated Mg2+ (greater than or equal to 1.2 mM) induce a transition from biphasic to monophasic kinetics. Comparison of the activation energy obtained for the fast biphasic step at low ionic strength (I0.069) shows excellent agreement with the values obtained at high ionic strength, low temperature and elevated Mg2+. From this observation it can be implied that the tubulin-containing reactant of the fast biphasic event is also the species that elongates microtubules during monophasic assembly. Second-order rate constants for biphasic assembly are 3.82(+/- 0.72) x 10(7) M-1.s-1 and 5.19(+/- 1.25) x 10(6) M-1.s-1, and for monophasic assembly the rate constant is 2.12(+/- 0.56) x 10(7) M-1.s-1. The microtubule number concentration is constant during elongation of microtubules for biphasic and monophasic assembly. 相似文献
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The thymic microenvironment. Characterization of in vitro differentiation of the IT26R21 rat thymic epithelial cell line 总被引:3,自引:0,他引:3
David F. Lobach Tsunetoshi Itoh Kay H. Singer Barton F. Haynes 《Differentiation; research in biological diversity》1987,34(1):50-59
We have previously postulated an in vivo pathway of thymic epithelial (TE) cell maturation in pre- and postnatal thymus, whereby endocrine medullary TE cells terminally differentiate to form Hassall's bodies. Epithelial-cell differentiation has been well documented in vitro using epidermal keratinocytes. Therefore, to characterize TE-cell differentiation in vitro, we observed clones of the rat TE cell line, IT26R21, after 4 and 14 days in culture. We found alterations in cell morphology, the cessation of cell proliferation, and the acquisition of a differentiation antigen defined by monoclonal antibody TE-19 (a marker of terminally differentiated epithelial cells). At light and electron microscopy, we detected progressive TE-cell stratification and squamous-cell formation between 4 and 14 days of culture. Autoradiography on day 14 showed that squamous TE cells in stratified layers did not incorporate tritiated thymidine, while surrounding smaller cells adhering to the substratum continued to synthesize DNA. At indirect immunofluorescence, only 3% of cells reacted with monoclonal antibody TE-19 at day 4, while on day 14, 22% of the TE cells were TE-19 positive (P less than 0.02). Antibody-TE-19 reactivity was limited to stratified, squamous TE cells. Additionally, we isolated a clone of the IT26R21 cell line that did not undergo these changes characteristic of TE cell differentiation. We conclude that IT26R21 TE cells are capable of undergoing programs of both terminal differentiation and cell renewal in vitro. 相似文献
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Adult Antarctic fur seals (Arctocephalus gazella) were immobilized with Zoletil® ( n = 172), ketamine ( n = 30), ketamine mixed with diazepam ( n = 23) and with ketamine mixed with xylazine ( n = 45). Response to all drugs was highly variable. There was a relationship between dose rate and level of immobilization in females given Zoletil® . Males were slightly more sensitive to Zoletil® than females but this could have been due to the greater body mass and lower mass-specific metabolic rate of males. The dose required to achieve a level of immobilization declined with greater body mass for Zoletil® and ketamine but not for ketamine-diatepam. Ketamine and ketamine-sedative mixtures commonly caused mild tremoring and occasionally caused convulsions. Neither reaction was seen with Zoletil® . Mean doses were, Zoletil® 1.5 mg/ kg, ketamine 6.9 mg/kg, ketamine-diazepam 6.3 mg/kg ketamine and 6.3 μg/kg diazepam, and ketamine-xylazine 7.3 mg/kg ketamine and 0.62 mg/ kg xylazine. Zoletil® performs at least as well on Antarctic fur seals as ketamine but it may cause respiratory depression. The dose of ketamine required for Antarctic fur seals was greater than for most other species of seals. 相似文献
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The coordination complex tris(4,7-diphenylphenanthroline)rhodium(III), Rh(DIP)3(3+), binds to and, upon photoactivation, cleaves both DNA strands near the base of a DNA cruciform. Sites of photoinduced double-stranded DNA cleavage by the rhodium complex map to regions containing cruciforms on closed circular pBR322, pColE1 and phi X174 (replicative form) DNAs. Neither cleavage nor binding by the metal complex, assayed using S1 nuclease, is found on the linear plasmid which lacks the extruded cruciform. High resolution mapping experiments reveal that Rh(DIP)3(3+) cleaves at a specific AT-rich site neighboring the stem of the minor cruciform on pBR322. The primary site of cleavage is found at position 3238 on the 3'-strand and 3250 on the 5'-strand and is remarkably specific. The pattern of cleavage, to one side only of the cruciform stem, indicates an asymmetry in the cruciform structure recognized by the complex. These results suggest that Rh(DIP)3(3+) may provide a useful reagent to probe cruciform sites. In addition, the high degree of specificity found in targeting the cruciform structure with this simple metal complex underscores the utility of shape-selection for the recognition of specific sites on a DNA strand. 相似文献