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Mutant
About: Mutant is a research topic. Over the lifetime, 74520 publications have been published within this topic receiving 3477079 citations.
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TL;DR: It is reported here that targeted disruption of the Hoxa-13 gene leads to a specific forelimb and hindlimb autopodal phenotype, distinct from that of theHoxd-13 paralogous gene inactivation, indicating that these genes act in a partially redundant manner.
Abstract: Members of the Abdominal-B-related Hox gene subfamily (belonging to homology groups 9 to 13) are coordinately expressed during limb bud development. Only two genes from homology group 13 (Hoxa-13 and Hoxd-13) are specifically expressed in the developing distal region (the autopod), which displays the most complex and evolutionarily flexible pattern among limb ‘segments’. We report here that targeted disruption of the Hoxa-13 gene leads to a specific forelimb and hindlimb autopodal phenotype, distinct from that of the Hoxd-13 paralogous gene inactivation. In both limbs, Hoxa-13 loss of function results in the lack of formation of the most anterior digit and to altered morphogenesis of some ‘preaxial’ carpal/tarsal elements. We have generated mice with all possible combinations of disrupted Hoxa-13 and/or Hoxd-13 alleles, which allowed us to investigate the degree of functional specificity versus redundancy of the corresponding gene products in the developing limb autopod. The phenotype of any double mutant was much more severe than the sum of the phenotypes seen in the corresponding single mutants, indicating that these genes act in a partially redundant manner. Our major findings were: (1) an abnormal autopodal phenotype in Hoxa-13+/−/Hoxd-13+/− double heterozygous mutants, which mostly consists of subsets of the alterations seen in each individual homozygous mutant, and therefore appears to result from quantitative, rather than qualitative, homeoprotein deficiency; (2) partly distinct alterations in mutants harboring a single non-disrupted allele of Hoxa-13 or Hoxd-13, indicating that the remaining reduced protein amounts are not functionally equivalent; (3) a polydactyly in the forelimbs of Hoxa-13+/−/Hoxd-13−/−double mutants, consisting of seven symmetrically arranged, truncated and mostly non-segmented digits; (4) an almost complete lack of chondrified condensations in the autopods of double homozygous mutants, showing that the activity of group 13 Hox gene products is essential for autopodal patterning in tetrapod limbs.
441 citations
TL;DR: The refined consensus hammerhead resulting from this work was used to identify potential hammerheads present in a variety of Escherichia coli gene sequences, suggesting that the hammerhead contains few, if any, replaceable tertiary interactions as are found in tRNA.
Abstract: A previously well-characterized hammerhead catalytic RNA consisting of a 24-nucleotide substrate and a 19-nucleotide ribozyme was used to perform an extensive mutagenesis study. The cleavage rates of 21 different substrate mutations and 24 different ribozyme mutations were determined. Only one of the three phylogenetically conserved base pairs but all nine of the conserved single-stranded residues in the central core are needed for self cleavage. In most cases the mutations did not alter the ability of the hammerhead to assemble into a bimolecular complex. In the few cases where mutant hammerheads did not assemble, it appeared to be the result of the mutation stabilizing an alternate substrate or ribozyme secondary structure. All combinations of mutant substrate and mutant ribozyme were less active than the corresponding single mutations, suggesting that the hammerhead contains few, if any, replaceable tertiary interactions as are found in tRNA. The refined consensus hammerhead resulting from this work was used to identify potential hammerheads present in a variety of Escherichia coli gene sequences.
440 citations
TL;DR: A genetic strategy to isolate the target of acidic activation domains of transcriptional activators based on toxicity in yeast cells of the chimeric activator, GAL4-VP16 concluded that ADA2 potentiates the activity of one class of acidicactivation domain but not a second class.
440 citations
TL;DR: Results indicate that the dsRNA binding protein DRB4 is required for proper ta-siRNA production, presumably by interacting with DCL4, an interaction analogous to that of HYL1 with D CL1 during miRNA production , and that TAS3 ta-SIRNAs are required for Proper leaf development through the action of AGO7/ZIPPY.
440 citations
TL;DR: It is suggested that currently available KIT inhibitors may be useful in treating neoplastic cells expressing KIT activated by its natural ligand or by RT activating mutations such as gastrointestinal stromal tumors but that neither compound is likely to be effective against SAHM.
439 citations