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B Capel

Publications and source records attributed to B Capel.

24 records · Page 2Linked to original sources
PubMed1990

Expression of a candidate sex-determining gene during mouse testis differentiation.

The development of a eutherian mammal as a male is a consequence of testis formation in the embryo, which is thought to be initiated by a gene on the Y chromosome. In the absence of this gene, ovaries are formed and female characteristics develop. Sex determination therefore hinges on the action of this testis-determining gene, known as Tdy in mice and TDF in humans. In the past, several genes proposed as candidates for Tdy/TDF have subsequently been dismissed on the grounds of inappropriate location or expression. We have recently described a candidate for Tdy, which maps to the minimum sex-determining region of the mouse Y chromosome. To examine further the involvement of this gene, Sry, in testis development, we have studied its expression in detail. Fetal expression of Sry is limited to the period in which testes begin to form. This expression is confined to gonadal tissue and does not require the presence of germ cells. Our observations strongly support a primary role for Sry in mouse sex determination.

Animals↗
PubMed1990

A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes.

A gene mapping to the sex-determining region of the mouse Y chromosome is deleted in a line of XY female mice mutant for Tdy, and is expressed at a stage during male gonadal development consistent with its having a role in testis determination. This gene is a member of a new family of at least five mouse genes, related by an amino-acid motif showing homology to other known or putative DNA-binding domains.

Amino Acid Sequence↗
PubMed1990

Long- and short-lived murine hematopoietic stem cell clones individually identified with retroviral integration markers.

The proliferative longevity of totipotent hematopoietic stem cells (THSC) is a limiting factor in normal hematopoiesis and in therapy by cell- or gene-replacement, but has not yet been ascertained. We have followed the long-term fate of individual clones of mouse THSC from fetal liver or adult bone marrow, after labeling in culture, followed by engraftment and serial transplantation in unirradiated W/Wv-C57BL/6 hosts. The ancestor cell of each clone and its mitotic progeny were uniquely identifiable retrospectively by the DNA integration pattern experimentally produced by replication-incompetent recombinant murine retroviruses. These viruses provided physiologically neutral markers. The marked clones proved to be derived from THSC, based on their contributions to a wide array of myeloid and lymphoid blood lineages in the hosts. The label also identified the target cells as the population displaying clonal succession. The various labeled stem cell clones proliferated for substantially different periods of time. The longest observed clone endured, after the original cell was marked, for at least 2 1/2 years--the equivalent of a mouse's lifetime. However, the results suggest that THSC clones are not all long-lived and that even the longest-lived ones may not be potentially immortal. Thus, the unpredictable lifespan of any given THSC clone indicates the desirability of introducing multiple clones in therapeutic transplants.

Animals↗
PubMed1989

Clonal contributions of small numbers of retrovirally marked hematopoietic stem cells engrafted in unirradiated neonatal W/Wv mice.

Mice were repopulated with small numbers of retrovirally marked hematopoietic cells operationally definable as totipotent hematopoietic stem cells, without engraftment of cells at later stages of hematopoiesis, in order to facilitate analysis of stem cell clonal histories. This result depended upon the use of unirradiated W/Wv newborn recipients. Before transplantation, viral integration markers were introduced during cocultivation of fetal liver or bone marrow cells with helper cell lines exporting defective recombinant murine retroviruses of the HHAM series. Omission of selection in culture [although the vector contained the bacterial neomycin-resistance (neo) gene] also limited the proportion of stem cells that were virally labeled. Under these conditions, engraftment was restricted to a small population of marked and unmarked normal donor stem cells, due to their competitive advantage over the corresponding defective cells of the mutant hosts. A relatively simple and coherent pattern emerged, of one or a few virally marked clones, in contrast to previous studies. In order to establish the totipotent hematopoietic stem cell identity of the engrafted cells, tissues were sampled for viral and inbred-strain markers for periods close to one year after transplantation. The virally labeled clones were characterized as stem cell clones by their extensive self-renewal and by formation of the wide range of myeloid and lymphoid lineages tested. Results clearly documented concurrent contributions of cohorts of stem cells to hematopoiesis. A given stem cell can increase or decrease its proliferative activity, become completely inactive or lost, or become active after a long latent period. The contribution of a single clone present in a particular lineage was usually between 5% and 20%.

Animals↗
PubMed1989

Neonatal W-mutant mice are favorable hosts for tracking development of marked hematopoietic stem cells.

Neonatal unirradiated mice of W-mutant genotypes, with a hematopoietic stem cell defect and anemia, were injected i.v. with normal fetal liver hematopoietic cells. Efficient, long-term engraftment occurred as a result of the competitive advantage to the donor stem cells. The frequency of engraftment and rate of repopulation characteristically diminish in the series W/Wv, Wf/Wf, and Wv/+, in which the severity of the endogenous defect is progressively less. H-2 compatibility is required in the inbred strain combinations examined; other histocompatibility loci play a minor role in some strain combinations. Engraftment is due to self-renewing hematopoietic stem cells ancestral to myeloid and lymphoid lineages. The more mildly defective mutants display much greater variability in the kinetics of repopulation--a result consistent with seeding by single, or very few, stem cells that form developing clones. Engraftment efficiency is reduced by prolonged culture of fetal liver cells during experimental infection by recombinant retroviruses; nevertheless, after 24 h in vitro to achieve retroviral marking, stem cells retain their ability to repopulate and develop in W/Wv neonates.

Animals↗