# DOSAGE COMPENSATION IN MAMMALS:  X-INACTIVATION

> **NIH NIH R37** · UNIVERSITY OF WASHINGTON · 1994 · $210,677

## Abstract

The general problem proposed for investigation is the analysis of mammalian
dosage compensation.  In particular the project will be concerned with the
molecular analysis of the X-inactivation mode of dosage compensation used
in humans, mice and a number of other mammalian forms.  Chromosomal dosage
control is critical to normal growth and development, and X-inactivation
brings about the essential equivalence of X-chromosome dosage in the
somatic cells of females and males.  No euploid fetus or individual with
two active X-chromosomes has been observed, suggesting that X-chromosome
dosage imbalance is lethal.

There are three stages in the X-inactivation process:  X-inactivation in
the extra embryonic lineage at blastocyst formation, X-inactivation in the
embryonic lineage during the very late blastocyst stage and reactivation of
the inactive X-chromosome in the germ cell lineage near the time of
oogenesis.  At the molecular level three sequential steps must be
considered:  initiation of inactivation at a single site or control center,
spreading of inactivation along the chromosome, and maintenance of the
inactivated state throughout the cells' somatic history.  Through the use
of various X-linked probes, in situ nick translation and high voltage
electron microscopy of sex chromatin, we will investigate these different
levels of developmental control of X-inactivation.

Initial studies will concentrate on differences between the active and
inactive X-chromosomes regarding specific X-linked genes, primarily the
phosphoglycerate kinase (PGK) and the replication enhancer plasmid genes.
X-linked cDNA and genomic probes will be used to look for chromatin
conformation and DNA modification differences between the active and
inactive X-chromosomes.  Materials to be studied will include cell cultures
varying in X-chromosome composition and murine tissues including
extra-embryonic and embryonic yolk sac tissues.  Chromatin configuration
will be investigated using nucleases and DNA modification will be studied
with restriction enzyme and sequence analyses.  In situ nick translation
and high voltage electron microscopy will be used to study sex chromatin
and a possible nuclear envelope attachment site of this structure.

## Key facts

- **NIH application ID:** 2197339
- **Project number:** 5R37HD016659-12
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** Stanley MICHAEL Gartler
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $210,677
- **Award type:** 5
- **Project period:** 1982-09-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197339

## Citation

> US National Institutes of Health, RePORTER application 2197339, DOSAGE COMPENSATION IN MAMMALS:  X-INACTIVATION (5R37HD016659-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197339. Licensed CC0.

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