# RETROVIRUSES AS PROBES FOR DEVELOPMENT

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 1994 · $238,691

## Abstract

Mutations affecting early development of the mouse embryo will be
generated using gene traps in embryonic stem (ES) cells. In this approach,
a reporter gene is introduced into ES cells by a retrovirus, but
expression of the reporter can only originate from the promoter of a gene
into which it has inserted.  Since the reporter gene used in these
experiments encodes beta-galactosidase activity, expression of the mutated
gene can be conveniently followed in heterozygous mice. The consequences
of gene disruption can be assessed by breeding the mice to homozygosity.
In previous work, 42 lines of mouse mutants have been generated, which
display a diversity of beta-galactosidase expression pattern during
development. A high proportion of overt phenotypes was observed among
these strains, since provirus insertion leads to embryonic lethality in 18
strains and to male sterility in two others. In one lethal strain, the
provirus has disrupted the gene which encodes the transcription factor
TEF1, leading to cardiac and central nervous system defects at
midgestation. We will continue to analyze these strains by histology to
understand the defects in mutant embryos, and by cloning the mutated gene.
We will also use gene traps to identify genes induced during development
in response to two types of factors thought to play critical roles in
early development: retinoic acid, a factor believed to have the properties
of a morphogen; and growth factors, whose receptors are protein tyrosine
kinases implicated in several classical mouse mutations affecting early
mouse development. It is anticipated that these studies will lead to the
identification of genes playing key roles in early mouse development, and
help identify, using genetics, critical components in specific signaling
pathways.

## Key facts

- **NIH application ID:** 2199332
- **Project number:** 2R01HD024875-06
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **SAM.gov UEI:** HMSNCM57QNR5
- **Principal Investigator:** Philippe M Soriano
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $238,691
- **Award type:** 2
- **Project period:** 1989-01-01 → 1998-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199332

## Citation

> US National Institutes of Health, RePORTER application 2199332, RETROVIRUSES AS PROBES FOR DEVELOPMENT (2R01HD024875-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199332. Licensed CC0.

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