# GENE REGULATION IN HEMOPOIESIS--TRANSGENIC APPROACHES

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 1994 · $263,569

## Abstract

The long-term objectives of this project are to elucidate:  (i) the
developmental regulation of the beta-globin gene family, and (ii) the role
of the nuclear factor GF-1 in the control of globin genes have long been
studied as a model system for gene regulation, and with a view to the
eventual treatment of hemoglobinopathies. Recently, the use of transgenic
mice has been instrumental in defining cis-acting elements involved in
temporal and tissue-specific control of the gene family.  Continuing our
studies of beta-globin regulation, we will employ two new strategies to
manipulate regulatory elements without disrupting the overall organization
of the locus, which appears to be functionally important.  First, the use
of yeast artificial chromosomes will make possible the cloning and
manipulation of the entire human gene cluster, and its subsequent transfer
into the mouse germ line, either in wild type form or after introducing
specific mutations. Second, gene targeting techniques will permit the
introduction of site-directed mutations into the endogenous beta-globin
locus in murine embryonic stem (ES) cells.  As well as testing models of
regulation, the latter experiments should result in the production of new
murine models of beta-thalassemia.  GF-1 is a DNA-binding protein found
specifically in erythroid, megakaryocyte and mast cells, which appears to
play a major role in the control of cell type-specific genes, and thus in
cell differentiation.  We propose to investigate the role of this nuclear
factor in the process of hemopoietic cell differentiation, and particularly
in globin gene expression, via several approaches:  first, we will study
the developmental consequences of a mutation that has disrupted the X-
linked GF-1 gene in a male ES cell line, by examining the ability of the
mutant cells to populate hemopoietic lineages in chimeric mice, and by
attempting to pass the mutation through the germ line; second, we will use
transgenic techniques to alter the level and pattern of GF-1 expression in
the developing mouse; and finally, we will perform experiments to define
the regulatory elements involved in the activation of the GF-1 gene itself,
which may represent a key step in the commitment of hemopoietic progenitors
to specific changes.

## Key facts

- **NIH application ID:** 2197516
- **Project number:** 5R01HD017704-12
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **SAM.gov UEI:** F4N1QNPB95M4
- **Principal Investigator:** FRANKLIN D COSTANTINI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $263,569
- **Award type:** 5
- **Project period:** 1983-04-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197516

## Citation

> US National Institutes of Health, RePORTER application 2197516, GENE REGULATION IN HEMOPOIESIS--TRANSGENIC APPROACHES (5R01HD017704-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197516. Licensed CC0.

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