# HYPERTHERMIA, HEAT-SHOCK RESPONSE, AND BIRTH DEFECTS

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1994 · $204,708

## Abstract

Hyperthermia is a well known teratogen in animals and a suspected
teratogen in humans. In addition to its teratogenic effects, acute
hyperthermia also induces a heat shock response characterized by
alterations in transcription and translation and the synthesis of heat
shock proteins (hsps). Furthermore, a variety of teratogens are capable of
inducing this heat shock, or more properly, stress response.  Our long
range goal, therefore, is to define the relationship between teratogen-
induced stress response and the induction of birth defects.  One of the
specific aims of this proposal is to use high resolution two-dimensional
gel electrophoresis coupled with computer-assisted image analysis to
examine the hypothesis that the induction of a stress response in the
mammalian embryo during the critical period of organogenesis can alter the
established program of activation and inactivation of genetic loci
essential for normal development.

Mild hyperthermia can also induce a thermotolerant state that protects
cells or embryos from the toxic effects of heat and other stress-inducing
agents. Although the mechanisms underlying thermotolerance are not well
understood, specific hsps (hsp 27 and 72) and antioxidant defenses
(glutathione, superoxide dismutase and glutathione peroxidase) have been
implicated.  A second specific aim, therefore, is to use antibodies,
cDNAs, enzyme assays, enzyme inhibitors and inducers to examine the
hypothesis that specific hsps and/or antioxidant defenses play a role in
the induction of thermotolerance in rodent embryos. Finally, we will
construct transgenic mice in which specific hsps are constitutively
expressed under the control of a beta-actin promoter to test the
hypothesis that hsps play a direct role in the induction of
thermotolerance in rodent embryos.

## Key facts

- **NIH application ID:** 2198449
- **Project number:** 2R01HD022095-06A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** PHILIP E MIRKES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $204,708
- **Award type:** 2
- **Project period:** 1987-08-01 → 1997-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198449

## Citation

> US National Institutes of Health, RePORTER application 2198449, HYPERTHERMIA, HEAT-SHOCK RESPONSE, AND BIRTH DEFECTS (2R01HD022095-06A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198449. Licensed CC0.

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