GATA-1-independent regulation of the expression of the erythropoietin receptor (EPO-R) gene in a human EPO-dependent cell line, UT-7 EPO.
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Cell Line↗
Biomedical subjects
G Migliaccio
Publications and source records attributed to G Migliaccio.
Biosynthesis and biochemical properties of the hepatitis C virus core protein.
The biosynthesis and biochemical properties of the putative nucleocapsid protein of hepatitis C virus (HCV) were investigated. RNA transcripts for cell-free translation were prepared from truncated form of the cDNA construct encoding the structural proteins of HCV. Processing of the translation products was dependent on microsomal membranes and signal recognition particle, suggesting that release of the 21-kDa core protein from the polyprotein precursor is mediated solely by the signal peptidase of the endoplasmic reticulum (ER) and is achieved by the removal of a putative signal sequence of approximately 18 residues located at its C terminus. The core protein was found to bind membranes in vitro and in transfected cells, as shown by centrifugation analysis of in vitro translation products and transfected-cell lysates. Immunofluorescence of transfected cells showed that the core protein colocalized with the E2 glycoprotein as well as with a cellular ER membrane marker. The nucleocapsid protein expressed by in vitro translation in rabbit reticulocyte lysates cosedimented with the large ribosomal subunit in sucrose gradients. The ribosome binding domain was mapped to the N-terminal region of the core protein. Moreover, the same region was shown to bind RNA in vitro, suggesting that cosedimentation of core protein with ribosomes may be mediated by the RNA binding of the nucleocapsid protein of HCV. These studies indicate that the HCV core protein is a cytoplasmic protein associated with the ER membranes and possesses RNA binding activity.
Amino Acid Sequence↗
Stem cell factor and the amplification of progenitor cells from CD34+ cord blood cells.
We have studied the frequency of colony-forming cells (CFC) in fetal and neonatal blood in comparison with adult blood and marrow. Fetal or neonatal blood contains at least as many CFC as adult marrow and higher numbers of the more primitive CFC--those CFC (mixed-cell CFC) giving rise to colonies composed of erythroid and myeloid cells. CD34+ cord blood cells (selected by one of several means) proliferate in culture over time and generate more CFC (from pre-CFC) and differentiated cells in response to stem cell factor (SCF) plus different hematopoietic growth factors. For its effect, SCF requires the synergistic action of erythropoietin (Epo), granulocyte colony-stimulating factor (G-CSF), or interleukin-3 (IL-3). In the presence of Epo or G-CSF, CFC and differentiated cells are generated for 15 days and are mainly erythroid or granulocytic, respectively. In contrast, SCF plus IL-3 generate multilineage CFC and differentiated cells for more than 1 month. When the conditions for these long-term suspension cultures were optimized, CFC and differentiated cells were generated for more than 2 months. At this time, CFC were no longer detectable, but cells continued to be generated, and the cells had a mast cell phenotype. These cells have been maintained and propagated for more than 8 months in the presence of IL-3 and SCF and may represent a useful tool to study human mast cell differentiation.
Aging↗
Expansion of human neonatal progenitor cells in vitro under serum-deprived conditions.
Over time CD34+ cells purified from human cord blood generate large numbers of progenitor and precursor cells in liquid culture under serum-deprived conditions if stimulated with a cocktail of growth factors which include stem cell factor (SCF). The ex vivo expansion observed in liquid cultures is not homogeneous over time but involves the recruitment of different cell compartments and can be triggered by different growth factor combinations. We have recognized at least three phases in these liquid cultures. Phase I spans the first 20 days of culture. In this phase, progenitor and precursor cells are generated from the progenitor cell compartment itself in response to SCF in combination with either IL-3, erythropoietin, or G-CSF. Phase II spans the second month of culture and involves the recruitment of less and less differentiated cells by IL-3 and SCF. Phase III spans from the third month on and results in the indefinite proliferation of human mast cells. These results raise caution on the biological equivalence of liquid culture en vivo expanded hematopoietic cells at different time points.
Antigens, CD↗
Unrelated placental blood for bone marrow reconstitution: organization of the placental blood program.
The usefulness of placental/umbilical cord blood as a source of stem cells for marrow reconstitution of HLA-matched siblings has now been extended to the unrelated-donor setting. The need for HLA-matched donor tissue makes it essential to have available a frozen inventory of ready-to-use placental blood units. The New York Blood Center's Placental Blood Project, designed to evaluate the practical feasibility of unrelated placental blood transplantation, consists of four basic modules: collection of placental blood, maternal samples and donor data, accession and testing for genetic and infectious disease markers, freezing placental blood units, and data organization and retrieval. Additional modules include a computerized HLA matching algorithm and organization of data about patients requiring transplantation, which may be best taken up by organ-sharing organizations in the future. In this report, we describe the organization and discuss the methods and overall experience after collecting the first 1,000 units and supplying the tissue for the first two unrelated-donor placental blood transplants.
Adult↗
Transcriptional and posttranscriptional regulation of the expression of the erythropoietin receptor gene in human erythropoietin-responsive cell lines.
With erythroid differentiation, committed progenitor cells acquire the ability to respond to erythropoietin (Epo). Epo interacts with target cells through the Epo receptor (Epo-R), whose expression is tightly regulated in a lineage-specific fashion. Epo-R expression is presumed to be progressively activated or repressed as cells progress along the erythroid or the myeloid pathway, respectively. Little is known of the mechanisms that underlie the erythroid-specific expression of the Epo-R gene. GATA-1, the major known transcription factor involved in Epo-R gene regulation, is not erythroid-specific. We have studied the regulation of the expression of the Epo-R gene in two related human Epo-responsive cell lines, UT-7 and UT-7 Epo. These lines express Epo-R at high levels because of amplification of the endogenous gene, which is apparently not rearranged. Treatment for 6 to 24 hours with the tumor promoter, phorbol myristate acetate (PMA), or 24 hours of growth factor starvation (Epo or granulocyte/macrophage colony-stimulating factor [GM-CSF]) decreased or increased the levels of Epo-R mRNA, respectively. In the case of growth factor starvation, the increase (approximately equal to threefold) in the level of Epo-R mRNA correlated directly with an increase in the rate of Epo-R gene transcription as measured by run-off assay. Both increases were observed as early as 3 hours after the growth factor was withdrawn and were reversible; levels of mRNA and transcription rates returned to baseline 3 hours after the cells were reexposed to growth factors. The changes in Epo-R expression after growth factor starvation were coordinated with changes in the level of expression of GATA-1 that were detected both at the mRNA and at the gene transcription level under these conditions (suggesting that GATA-1 was responsible for this upregulation). During PMA treatment, after a transient increase in Epo-R mRNA at 1 hour, a progressive decline in the level of Epo-R mRNA was observed; the level of Epo-R mRNA decreased by 50%, and fell below the level of detection by 6 and 24 hours, respectively. This decrement was explained in part by a fourfold reduction in the rate of gene transcription as well as a reduction (measured as levels of Epo-R mRNA in the presence of actinomycin D) in mRNA stability. The changes in transcription rate occurred in the absence of changes in the level of GATA-1 binding activity.(ABSTRACT TRUNCATED AT 400 WORDS)
Blotting, Northern↗
Erythropoietin-specific cell cycle progression in erythroid subclones of the interleukin-3-dependent cell line 32D.
Recently, a variety of growth factor-dependent subclones of the murine interleukin-3 (IL-3)-dependent cell line 32D have been isolated. These subclones include those dependent for growth on erythropoietin (Epo) (32D Epo), granulocyte-macrophage colony-stimulating factor (GM-CSF) (32D GM), or granulocyte colony-stimulating factor (G-CSF) (32D G). 32D Epo1.1 is a revertant of 32D Epo and is capable of growing in IL-3. These cell lines express the differentiation program appropriate to the specific growth factor and depend on the growth factors not only for proliferation but also for survival. To determine how the signal for proliferation is triggered by various growth factors, we examined the DNA histograms and the expression of cell cycle-specific genes in the different cell lines. The cell cycle-specific genes analyzed were myc (early G1), myb (late G1), and the structural genes for the calcium-binding protein 2A9 (middle G1) and histone H3 (G1-S boundary). The DNA histogram analysis of cells in the logarithmic phase of growth showed that approximately 40% of 32D, 32D GM, 32D G, and 32D Epo1.1 (growing in IL-3) were cells with a 2N DNA content (and therefore in G0/G1), and another 40% have a DNA content intermediate between 2N and 4N (in S phase). In contrast, 32D Epo and 32D Epo1.1 (growing in Epo) had fewer cells in the G0/G1 phase of the cell cycle compared with the number of cells that were in the S phase (19% to 31% v 69% to 78%, respectively). Because all the cell lines have comparable doubling times (15 to 18 hours), the cell distribution among the phases of the cell cycle is proportional to the length of the phase. Therefore, cells growing in IL-3 (32D and 32D Epo1.1), GM-CSF (32D GM), or G-CSF (32D G) progress along the cycle in a manner typical of previously reported nontransformed cell lines. In contrast, cells growing in Epo (32D Epo or 32D Epo1.1) spend relatively less time in G0/G1 and correspondingly more time in S. These data were confirmed by the analysis of the tritiated thymidine (3H-TdR) suicide rate and of the expression of cell cycle-specific genes. The 32D and 32D Epo1.1 cells growing in IL-3 had a suicide rate of congruent to 50%, whereas the suicide rate of 32D Epo and 32D Epo1.1 growing in Epo was higher than 75%.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Induction of the murine "W phenotype" in long-term cultures of human cord blood cells by c-kit antisense oligomers.
The murine white (W) spotting locus is the site of the c-kit gene and encodes a tyrosine kinase receptor while the complementary Steel (Sl) locus encodes its ligand. Mutations at either locus have profound effects on hematopoiesis, particularly erythroid and mast cell proliferation. We added c-kit antisense oligonucleotides to long-term suspension cultures of enriched human umbilical cord progenitor cells. This resulted in the suppression of c-kit gene expression and the preferential suppression of the generation of erythroid burst-forming cells (BFU-E) which extended over the life of the culture (3 weeks). The results provide an in vitro model of the "W phenotype" in human hematopoiesis and confirm the importance of c-kit gene function in early erythropoiesis. Because the generation of BFU-E was suppressed even after c-kit gene expression had recovered, this gene product may be critical to the erythroid commitment process.
Animals↗
Aspects of the biology of the neonatal hematopoietic stem cell.
We have studied the frequency of colony forming cells (CFC) in fetal and neonatal blood in comparison with adult blood and marrow. Fetal/neonatal blood contains at least as many CFC as adult marrow and higher numbers of the more primitive CFC--those CFC giving rise to colonies composed of erythroid and myeloid cells. CD34+ cord blood cells (selected either by sorting, panning or affinity chromatography) proliferate in culture over time and generate more CFC (from pre-CFC) and differentiated cells in response to Steel factor plus different hematopoietic growth factors. Steel factor is unable to stimulate cell growth by itself under serum-deprived conditions and requires the synergistic action of erythropoietin (Epo), granulocyte colony stimulating factor (G-CSF) or interleukin 3 (IL-3). In the presence of Epo or G-CSF, CFC and differentiated cells are generated for 15 days and are mainly erythroid or granulocytic, respectively. In contrast, Steel factor plus IL-3 generates multilineage CFC and differentiated cells for more than one month. When the conditions for these long-term suspension cultures were optimized (37 degrees C, regular refeeding with fresh growth factors and media without changing the flask), CFC and differentiated cells were generated for more than two months. At this time, CFC were no longer detectable and all cells had a mast cell phenotype. These cells have been maintained and propagated for more than eight months in the presence of IL-3 and Steel factor and may represent a useful tool to study human mast cell differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The generation of colony-forming cells (CFC) and the expansion of hematopoiesis in cultures of human cord blood cells is dependent on the presence of stem cell factor (SCF).
We have analyzed the effect of stem cell factor (SCF), alone or in combination with other growth factors, on the generation of colony-forming cells (CFC) and on the expansion of hematopoiesis in vitro from light density, soybean agglutinin-, CD34+ cord blood cells under serum-deprived conditions. The growth factors were either added only once at the onset of the culture or added every few days when the cultures were demidepopulated and refed with fresh medium. No growth factor, alone, generated CFC or expanded hematopoiesis under these conditions. However, SCF, in combination with interleukin 3 (IL-3) or with "late-acting factors" (granulocyte colony-stimulating factor (G-CSF) or erythropoietin (Epo)), generated large numbers of mature cells as well as CFC. The number of CFC generated depended on the refeeding procedure adopted. In cultures never refed, the CFC numbers increased from < 160 CFC/culture at day 0 to > 3000 CFC at day 10. The CFC numbers stayed above the input levels for 25 days before declining. Almost no CFC were detectable after one month. In contrast, in cultures regularly refed, CFC were detectable for at least 40 days. The lineages of the mature cells and the types of CFC generated varied with the different growth factors. In the presence of SCF plus IL-3, erythroid burst-forming cells (BFU-E) and granulocyte/macrophage colony-forming cells (GM-CFC) were generated and erythroid as well as myelomonocytic precursors were present among the differentiated cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Antigens, CD↗
The biology of stem cell factor, a new hematopoietic growth factor involved in stem cell regulation.
Recently, a new hematopoietic growth factor, stem cell factor, the ligand for the c-kit-proto-oncogene, has been cloned. The gene for this factor or for its receptor are deleted in two well known series of mice mutants which display pleiotropic stem cell defects. Therefore, this factor supposedly plays an important role in stem cell biology. This paper reviews some of the elegant genetic work which led to the discovery of the factor and of its receptor, the biological effects that this factor exerts in the hematopoietic system in normal individuals and in patients with Diamond-Blackfan anemia and speculates on some of its potential clinical applications.
Anemia↗
Long-term generation of colony-forming cells (CFC) from CD34+ human umbilical cord blood cells.
Human umbilical cord blood cells represent a potential alternative to bone marrow as a source of stem and progenitor cells for allogeneic transplantation. Therefore, many studies are underway to evaluate the number of cord blood stem cells and their amplification potential. We analyze here the amplification potential of CD34+ cord blood cells in liquid cultures stimulated with stem cell factor (SCF) in combination with interleukin-3 (IL-3), erythropoietin (Epo) or granulocyte colony-stimulating factor (G-CSF) under serum-deprived conditions. We report that under certain circumstances (stimulation with SCF and IL-3, replacing of the medium and growth factors every 3-4 days, no change of the initial culture flask, 37 degrees C as incubation temperature), CD34+ cells give rise to differentiated cells and progenitor cells for more than two months. During this period, more than 10(10) differentiated cells and 10(6) progenitor cells are generated from 0.25-1 x 10(4) CD34+ cells in the absence of a stromal layer. These data highlight the high proliferative and differentiative potential of cord blood stem cells and, because the culture procedures are relatively simple and do not require a stromal layer, open the way to the clinical use of ex vivo stem cell expansion.
Animals↗
Dependence for the proliferative response to erythropoietin on an established erythroid differentiation program in a human hematopoietic cell line, UT-7.
Erythroid differentiation involves the activation of a number of erythroid-specific genes, most of which, including the globin genes and the erythropoietin receptor (Epo-R) gene, are, at least in part, regulated by the transcription factor GATA-1. In order to understand the relationship, if any, between expression of GATA-1, response to Epo and erythroid differentiation, we analyzed the expression of GATA-1, Epo-R and globin genes in an Epo-dependent human cell line, UT-7 Epo. The results were compared to those obtained with the parental granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cell line, UT-7, which has a predominantly megakaryoblastic phenotype and is unable to proliferate continuously in the presence of Epo. UT-7 Epo and UT-7 expressed similar levels of GATA-1 mRNA and binding activity. The two lines also expressed comparable levels of Epo-R mRNA while the number of Epo-binding sites on UT-7 Epo cells was one-sixth the number of UT-7 cells (2400 +/- 3 vs. 13,800 +/- 300). This difference in the number of binding sites could be due to differences in cell surface (UT-7 cells are 20% smaller than the parental UT-7 cells) or in receptor turnover. By Northern analysis, UT-7 cells expressed detectable levels of beta- and gamma-globin but not alpha-globin. In comparison, UT-7 Epo cells expressed alpha-globin and higher levels of gamma-globin (5-fold) and beta-globin (from barely to clearly detectable). Globin chains (alpha, beta and gamma) were clearly detectable by affinity chromatography in UT-7 Epo but not in UT-7 cells. The frequency of the cells which expressed beta- and gamma-globin genes in the two cell populations was measured by immunofluorescence with beta- and gamma-specific antibodies. The number of gamma-positive cells and their fluorescence intensity were higher in UT-7 Epo than in UT-7 cells (0 to 17% barely positive cells and 23 to 40% clearly positive cells, respectively), indicating that the increase in globin mRNA observed in UT-7 Epo is due to both an increase of gene expression per cell and an increase in numbers of cells containing gamma-globin. The levels of GATA-1, Epo-R and globin mRNA expressed were not affected by a 24-hour incubation of either cell line with Epo, GM-CSF or interleukin-3 (IL-3).(ABSTRACT TRUNCATED AT 400 WORDS)
Blotting, Northern↗
Long-term generation of colony-forming cells in liquid culture of CD34+ cord blood cells in the presence of recombinant human stem cell factor.
Human cord blood was used as a source of progenitor and stem cells to evaluate the effect of recombinant human stem-cell factor (SCF) on colony formation and the generation of colony-forming cells (CFC) under highly defined, serum-deprived conditions. SCF interacted with a number of hematopoietic growth factors to stimulate colony growth and was particularly effective in stimulating the formation of mixed-cell colonies from CD34+ soybean agglutinin negative (SBA-) cells. In suspension culture of CD34+, SBA- cells, SCF alone was unable to maintain cell numbers or CFC but, in combination with interleukin-3 (IL-3), increased input numbers of cells by 10-fold and increased CFC of all kinds by nearly 20-fold. This included erythroid burst-forming cells (BFU-E), granulocyte/macrophage (GM) CFC, and mixed-cell CFC. In contrast, CD34- SBA- cells neither gave rise to CFC nor were maintained by combinations of growth factors including SCF. SCF interacted with erythropoietin (Epo) and granulocyte colony-stimulating factor (G-CSF) to maintain large numbers of cells as well as to generate a twofold to threefold increase in CFC in the case of Epo, and a 10-fold increase in CFC in the case of G-CSF. With Epo, the predominant CFC generated were BFU-E and erythroid CFC and many of the cells in suspension were erythroblasts. In contrast, SCF plus G-CSF resulted in large numbers of granulocytes at various stages of maturation and the CFC generated were almost exclusively granulocytic-CFC. IL-1 and IL-6, alone or in combination with SCF, showed little or no ability to increase cell numbers or generate CFC. In summary, SCF interacts with a variety of hematopoietic growth factors to promote colony formation, particularly mixed-cell colony formation, and also, in suspension culture, SCF interacts with IL-3, G-CSF, and Epo to generate large numbers of differentiated cells as well as a variety of CFC for up to 1 month.
Antigens, CD↗
Biosynthesis and oligosaccharide structure of human CD8 glycoprotein expressed in a rat epithelial cell line.
The biosynthesis, post-translational modifications, and oligosaccharide structure of human CD8 glycoprotein have been studied in transfected rat epithelial cells. These cells synthesized and expressed on the plasma membrane high amounts of CD8 in a homodimeric form stabilized by a disulfide bridge. Three different CD8 forms were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis after metabolic labeling and immunoprecipitation: a newly synthesized, unglycosylated 27-kDa (CD8u), a palmitylated and initially O-glycosylated 29-kDa (CD8i), and the mature, terminally glycosylated 32-34-kDa doublet (CD8m). CD8i is a transient intermediate form between CD8u and CD8m: characterization of carbohydrate moiety of [3H]glucosamine-labeled CD8i showed that it comprises for the vast majority non-elongated O-linked GalNAc closely spaced on the peptide backbone. Structural analysis of oligosaccharides released by mild alkaline borohydride treatment from the [3H]glucosamine-labeled CD8 34-kDa form showed that the neutral tetrasaccharide Gal beta 1,4GlcNAc beta 1,6(Gal beta 1,3)GalNAcOH, and an homologous monosialylated pentasaccharide, predominate; the disialylated NeuAc2,3Gal beta 1,3(NeuAc alpha 2,6) GalNAcOH tetrasaccharide appeared to be poorly present. In the CD8 32-kDa form the neutral tetrasaccharide was by far the prominent O-linked chain, and no disialyloligosaccharides were identified. These results indicate that the maturation of CD8 glycoprotein in transfected rat epithelial cells results in the formation of branched O-linked oligosaccharides and that a higher degree of sialylation is responsible for the production of the heavier 34-kDa form.
Animals↗
Expression of the interleukin-3 and granulocyte-macrophage colony-stimulating factor genes in Friend spleen focus-forming virus-induced erythroleukemia.
Friend spleen focus-forming virus (F-SFFV) is a replication-defective retrovirus that induces a multistage erythroleukemia in mice. In the first stage, expression of the SFFV envelope glycoprotein results in erythroid hyperplasia. Subsequently, the F-SFFV integrates near the Spi-1 gene and activates its expression, resulting in immortalized cells that represent a second stage in the disease process. We report here that media conditioned by erythroleukemia cell lines or leukemic spleen cells induced by the polycythemia-inducing strain of F-SFFV (F-SFFVp), but not medium conditioned by SFFVp-induced hyperplastic spleens, promote the proliferation of normal granulocyte-macrophage progenitor cells and of granulocyte-macrophage colony-stimulating factor (GM-CSF)- and/or interleukin-3 (IL-3)-dependent cell lines. The colony-stimulating activity of the conditioned media from four of five of the lines studied was neutralized by antibodies specific for IL-3 and/or GM-CSF, and IL-3 and GM-CSF-specific mRNA could be detected in the cells after amplification by the polymerase chain reaction. No rearrangements of the IL-3 or GM-CSF genes were observed by Southern blot analysis. However, as previously shown for SFFV-induced cell lines, the Spi-1 gene was expressed in all of these cells. Because the Spi-1 gene encodes a transcription factor whose cognate sequences are present in the promoter region of many hematopoietic growth factor genes, including IL-3 and GM-CSF, Spi-1 activation may be inducing the expression of these genes.
Animals↗
Production of granulocyte colony-stimulating factor and granulocyte/macrophage-colony-stimulating factor after interleukin-1 stimulation of marrow stromal cell cultures from normal or aplastic anemia donors.
We have studied stromal cell function in naive or interleukin-1 (IL-1)-stimulated (100 pg/ml) long-term marrow cultures (LTC) from 12 normal donors and 21 patients with severe aplastic anemia (AA). Conditioned media (CM) from normal LTC contained levels of erythroid burst-promoting activity (BPA) and granulocyte/macrophage (GM) colony-stimulating activity (CSA) comparable to those previously described (Migliaccio et al., [1990] Blood, 75:305-312). The addition of IL-1 to these cultures increased the level of CSA and, specifically, of granulocyte colony-stimulating factor (G-CSF) released. Anti-GM-CSF antibody neutralized BPA and CSA in normal naive LTC CM but only the CSA in the CM from IL-1-stimulated LTC. Since the concentrations of GM-CSF, as detected with a specific immunoassay, did not increase after IL-1 treatment, these data suggest that IL-1-stimulated cultures contain an unidentified growth factor having BPA. CM from AA stromal cells contained levels of CSA comparable to those observed in normal stromal cell CM but had significantly lower levels of BPA. Neither anti-GM-CSF nor anti-IL-3 antibodies neutralized the BPA in AA stromal cell CM. This activity may be related to that found in the CM of IL-1-treated normal stromal cells. In nearly 50% of stromal cell cultures of AA patients, addition of IL-1 failed to increase the BPA, CSA, or G-CSF. The presence of an inhibitor in naive or IL-1-treated AA stromal cell CM was excluded by adding the CM to IL-3-stimulated cultures. These findings suggest that G-CSF and GM-CSF genes are differentially regulated in the marrow microenvironment. Furthermore, a marrow microenvironment, deficient in BPA production and, in some cases, unresponsive to IL-1 could contribute to marrow failure in some patients with AA.
Anemia, Aplastic↗
Induced crossing-over in Drosophila melanogaster germ cells of DNA repair-proficient and repair-deficient (mei-9L1) males following larval feeding with 5-azacytidine and mitomycin C.
The effects of 5-azacytidine (5-AZ) and mitomycin C (MMC), administered by larval feeding, on crossing-over were measured in Drosophila melanogaster male germ cells of a DNA repair-proficient and a repair-deficient (mei-9L1) strain. Both 5-AZ and MMC are effective inducers of male crossing-over. The estimated number of induced recombination events was higher in repair-proficient than in mei-9L1 males. The apparently lower sensitivity of mei-9L1 males to crossing-over induction may be the result of an incomplete crossing-over process.
Animals↗