# GENES THAT CONTROL EMBRYONIC DEVELOPMENT IN THE MOUSE

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1994 · $239,194

## Abstract

The ultimate goal of this proposal is to identify, characterize, and
study the function of genes involved in critical steps in early
mammalian development.  Initially, we will focus our attention on the
Evx-1 gene, a mouse cognate of the Drosophila homeobox-containing even-
skipped gene. Based on the observation that Evx-1 is expressed in a
gradient in the primitive streak, we have hypothesized that Evx-1
functions in a dose-dependent fashion to provide dorso-ventral
patterning of the newly formed mesoderm. To test this hypothesis we
will determine the consequences of expressing Evx-1 RNA at high levels
throughout the primitive streak, thereby ablating the gradient of Evx-1
RNA that is normally observed. We will also determine the consequences
of ablating Evx-1 gene function, by creating embryos homozygous for a
null allele of Evx-I. In addition, we will identify the genomic
sequences that determine the tissue-specificity of Evx-1 expression in
the developing embryo. A second major goal is to identify and isolate
the gene encoding a molecule, VE-1, that is expressed in the visceral
endoderm overlying the future anterior region of the embryo during the
early post-implantation stages of development. Our long-term goal is
to determine the function of this earliest known marker of A-P polarity
in mouse embryogenesis.

In the course of pursuing these experiments, we propose to test the
efficacy of a new method (the cre/lox "binary" transgenic mouse system)
based on DNA recombination for manipulating gene expression in vivo.
In these experiments the desired effect, e.g. ectopic gene expression,
is achieved by mating mice of two different transgenic strains. One
(the "target" mouse) carries a target transgene that is innocuous but
has the potential to cause the desired effect, and the other (the
"effector" mouse) carries a DNA recombinase capable of altering the
target transgene so that it can produce the desired effect. Because the
target transgene has no effect prior to recombination, and the effector
(DNA recombinase) alone has no phenotype, both target and effector mice
are normal. However, in offspring that inherit both transgenes the
target transgene is altered by the effector, producing the desired
phenotype. Specifically, the system we propose to test employs the cre
gene of bacteriophage P1 as the effector. If this approach is
successful, we propose further experiments aimed at increasing its
versatility, by generating a standard target mouse strain that can be
used with a variable effector strain to produce a new lineage map of
the mouse, based on gene expression rather than anatomical position.
We hope that in the long-term these experiments will not only lead to
greater insights into the basic mechanisms controlling embryonic
development, but will make a contribution towards the development of
a new genre of transgenic mouse technology.

## Key facts

- **NIH application ID:** 2199505
- **Project number:** 2R01HD025331-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** GAIL R. MARTIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $239,194
- **Award type:** 2
- **Project period:** 1989-06-01 → 1999-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199505

## Citation

> US National Institutes of Health, RePORTER application 2199505, GENES THAT CONTROL EMBRYONIC DEVELOPMENT IN THE MOUSE (2R01HD025331-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199505. Licensed CC0.

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