# REGULATION AND FUNCTION OF KERATINS IN THE EPIDERMIS

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 1994 · $255,690

## Abstract

Changes in keratin gene expression are closely associated with changes
in the differentiation state of the keratinocyte.  For instance, the
induction of the differentiation-specific keratins, K1 and K10 can
already be observed in basal cells that have lost their proliferative
capacity and are about to migrate to the spinous layer.  The induction
of K6 on the other hand, occurs rapidly in interfollicular epidermis that
has suffered trauma and remains induced as long as the traumatizing
stimulus persists.  In both cases the induction of new keratin types is
associated with a down regulation of the previous keratin genes with the
newly induced proteins replacing the pre-existing network.  As the
central rod domains of these keratins are remarkably similar, the
significance of new keratin expression probably lies in the expression
of a new set of end-domains.  However, the exact role of the end-domains
in keratin filament biology and their impact on the function of the
epidermis remains to be determined.  An understanding of the molecular
mechanism regulating expression of these keratin genes together with
information on the biological roles of the various end-domains will
provide insights into keratinocyte function in both normal and abnormal
states.  Both in vivo transgenic and in vitro tissue culture techniques
will be used to explore the regulation of K1.  The transgenic
experimental system will be utilized to identify those elements required
for correct tissue, developmental and differentiation specific
expression.  The micro analysis of these elements will be examined by
insertion of putative regulatory regions in reporter constructs, followed
by transfection into primary epidermal keratinocytes.  Proteins that
interact with these elements will be characterized and those that are
unique to keratinocytes will be cloned.  To explore the role of the
unique end-domains on keratinocyte function, various mutations will be
engineered into the N and C termini of K6 and introduced into the
germline of transgenic mice.  These end-domain mutations, as well as
constructs which swap the end-domains between keratins, are designed not
only to gain insights into end-domain function, but also to create mouse
models of human skin disorders.  This reverse genetics approach may
potentially identify other keratin disorder in man.  Finally, the animal
models, produced as a results of these studies, can be exploited for the
assessment of gene therapy protocols in the amelioration of these skin
diseases.

## Key facts

- **NIH application ID:** 2199594
- **Project number:** 2R01HD025479-06
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **SAM.gov UEI:** FXKMA43NTV21
- **Principal Investigator:** Dennis Roop
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $255,690
- **Award type:** 2
- **Project period:** 1989-04-01 → 1999-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199594

## Citation

> US National Institutes of Health, RePORTER application 2199594, REGULATION AND FUNCTION OF KERATINS IN THE EPIDERMIS (2R01HD025479-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199594. Licensed CC0.

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