# MOLECULAR GENETICS OF THERMOGENESIS

> **NIH NIH R01** · JACKSON LABORATORY · 1994 · $272,679

## Abstract

Obesity is viewed as an imbalance in the regulation of energy input
and energy expenditure of an individual.  The many components in energy
homeostasis, i.e. food intake, physical activity, basal activity and heat
production, make obesity a complex problem.  We seek to understand the
role of non-shivering thermogenesis, the process for heat production by
brown fat, in this process.  The capacity for non-shivering thermogenesis
depends on activation of the mitochondrial uncoupling protein (UCP),
lipolysis, and respiration by sympathetic innervation and the amount of
brown fat in an individual.  The first specific aim seeks to identify the
cis-acting DNA sequences which restrict expression of the Ucp gene to
brown fat only and stimulate its expression in response to cold.  The
primary focus in this specific aim is to identify sequences, which
interact with a brown fat specific transcription factor, by a combination
of transient expression, gel retardation and DNA footprinting analyses of
nested deletions of the promoter region and DNAase 1 sensitive regions.
The second specific aim seeks to clone the transcription factor from a
lambda gt11 expression cDNA library.  The cDNA clones will then be used
in the third specific aim to determine whether a brown fat specific
transcription factor can induce brown fat differentiation from a white
fat cell lineage, by analogy with the role that a muscle transcription
factor, Myo D, has in inducing muscle cell differentiation, The fourth
specific aim will evaluate the in vivo function of the transcripton
factor by inactivating the endogenous gene in embryonic stem cells by
homologous recombination.  Cells carrying the mutated gene will then be
introduced into the animal by microinjection into blastocysts to obtain
live offspring with a mutated gene.

## Key facts

- **NIH application ID:** 2196594
- **Project number:** 5R01HD008431-20
- **Recipient organization:** JACKSON LABORATORY
- **SAM.gov UEI:** XR6LMXNKDJJ1
- **Principal Investigator:** Leslie Paul Kozak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $272,679
- **Award type:** 5
- **Project period:** 1977-02-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196594

## Citation

> US National Institutes of Health, RePORTER application 2196594, MOLECULAR GENETICS OF THERMOGENESIS (5R01HD008431-20). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196594. Licensed CC0.

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