[Federal Register Volume 65, Number 225 (Tuesday, November 21, 2000)]
[Notices]
[Pages 69949-69950]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-29716]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, DHHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by agencies of the U.S. 
Government and are available for licensing in the U.S. in accordance 
with 35 U.S.C. 207 to achieve expeditious commercialization of results 
of federally-funded research and development. Foreign patent 
applications are filed on selected inventions to extend market coverage 
for companies and may also be available for licensing.

ADDRESSES: Licensing information and copies of the U.S. patent 
applications listed below may be obtained by writing to the indicated 
licensing contact at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

Enhanced Homologous Recombination Mediated by Lambda Recombination 
Proteins

    Donald L. Court, Daiguan Yu, E-Chaing Lee, Hilary Ellis, Nancy A. 
Jenkins, Neal G. Copeland (NCI), DHHS Reference No. E-177-00/0 filed 14 
Aug 2000, Licensing Contact: Dennis Penn; 301/496-7056 ext. 211; e-
mail: <a href="/cdn-cgi/l/email-protection#f484919a9a90b49b90da9a9d9cda939b82"><span class="__cf_email__" data-cfemail="90e0f5fefef4d0fff4befef9f8bef7ffe6">[email protected]</span></a>.
    The present invention concerns methods to enhance homologous 
recombination in bacteria and eukaryotic cells using recombination 
proteins derived from bacteriophage lambda. It also concerns methods 
for promoting homologous recombination using other recombination 
proteins.
    Concerted use of restriction endonucleases and DNA ligases allows 
in vitro recombination of DNA sequences. The recombinant DNA generated 
by restriction and ligation may be amplified in an appropriate 
microorganism such as E. coli, and used for diverse purposes including 
gene therapy. However, the restriction-ligation approach has two 
practical limitations: first, DNA molecules can be precisely combined 
only if convenient restriction sites are available; second, because 
useful restriction sites often repeat in a long stretch of DNA, the 
size of DNA fragments that can be manipulated are limited, usually to 
less than about 20 kilobases.
    Homologous recombination, generally defined as an exchange of 
homologous segments anywhere along a length of two DNA molecules, 
provides an alternative method for engineering DNA. In generating 
recombinant DNA with homologous recombination, a microorganism such as 
E. coli, or a eukaryotic cell such as a yeast or vertebrate cell, is 
transformed with an exogenous strand of DNA. The center of the 
exogenous DNA contains the desired transgene, whereas each flank 
contains a segment of homology with the cell's DNA. The exogenous DNA 
is introduced into the cell with standard techniques such as 
electroporation or calcium phosphate-mediated transfection, and 
recombines into the cell's DNA, for example with the assistance of 
recombination-promoting proteins in the cell.
    In generating recombinant DNA by homologous recombination, it is 
often advantageous to work with short linear segments of DNA. For 
example, a mutation may be introduced into a linear segment of DNA 
using polymerase chain reaction (PCR) techniques. Under proper 
circumstances, the mutation may then be introduced into cellular DNA by 
homologous recombination. Such short linear DNA segments can transform 
yeast, but subsequent manipulation of recombinant DNA in yeast is 
laborious. It is generally easier to work in bacteria, but linear DNA 
fragments do not readily transform bacteria (due in part to degradation 
by bacterial exonucleases). Accordingly, recombinants are rare, require 
special poorly-growing strains (such as RecBCD-strains) and generally 
require thousands of base pairs of homology. This invention teaches an 
improved method of promoting homologous recombination in bacteria.
    In eukaryotic cells, targeted homologous recombination provides a 
basis for targeting and altering essentially any desired sequence in a 
duplex DNA molecule, such as targeting a DNA sequence in a chromosome 
for replacement by another sequence. This invention teaches methods 
useful for treating human genetic diseases, the creation of transgenic 
animals, or modifying the germline of other organisms.

Amelogenin Knockout Mice and Use as Models for Tooth Disease

    Dr. Ashok Kulkarni et al. (NIDCR), DHHS Reference No. E-167-00/0, 
Licensing Contact: John Rambosek; 301/

[[Page 69950]]

496-7056 ext. 270; e-mail: <a href="/cdn-cgi/l/email-protection#0173606c636e72646b416e652f6f68692f666e77"><span class="__cf_email__" data-cfemail="2f5d4e424d405c4a456f404b0141464701484059">[email protected]</span></a>.
    This technology relates to transgenic knockout mice that may serve 
as an animal model for dental disease. Using gene-targeting techniques, 
mice have been created which are disrupted for the amelogenin gene. 
These mice lack the amelogenin protein, which is normally expressed 
only in the teeth. Since these mice lack this protein, they are 
expected to mimic an inherited tooth disorder called ``amelogenesis 
imperfecta (AI)''. AI is an inherited condition that is transmitted as 
a dominant trait and causes the enamel of the tooth to be soft and thin 
resulting in discoloration, disintegration and disfigurement of the 
teeth. The damaged teeth are also susceptible to decay. The amelogenin 
knockout mice display an interesting tooth phenotype. Their maxillary 
incisors are chalky white in color and opaque in appearance.
    These changes are associated with mild attrition of incisor tips 
and molar cusps. Detailed analysis of this phenotype is in progress. 
The amelogenin knockout mice may be used as an animal model to develop 
therapeutic approaches to AI.

Transgenic Mouse Model for Tooth Disorders Such as Dentin Dysplasia 
and Dentinogenesis Imperfecta

    Drs. Thyagarajan, Sreenath, and Kulkarni (NIDCR), DHHS Reference 
No. E-150-00/0, Licensing Contact: John Rambosek, Ph.D.; 301/496-7056; 
e-mail: <a href="/cdn-cgi/l/email-protection#9deffcf0fff2eef8f7ddf2f9b3f3f4f5b3faf2eb"><span class="__cf_email__" data-cfemail="ccbeada1aea3bfa9a68ca3a8e2a2a5a4e2aba3ba">[email protected]</span></a>.
    This technology describes transgenic mice that selectively 
overexpress transforming growth factor beta-1 (TGF-beta1) in 
odontoblast and ameloblast cells of teeth. Ameloblasts mainly make 
enamel, whereas odontoblasts make dentin. These transgenic mice mimic 
dental symptoms similar to those seen in common tooth disorders such as 
dentin dysplasia and dentinogenesis imperfecta. Both of these human 
dentin defects are inherited in an autosomal dominant manner and appear 
to be caused by abnormal dentin production by odontoblasts and 
associated poor mineralization of the dentin matrix. In both diseases, 
teeth are discolored and fractured, causing difficulties in eating 
food. Experimentally, these mice display discolored and fractured teeth 
with defective dentin. This transgenic mice model will be valuable to 
advance our understanding of the molecular pathogenesis underlying 
dentin dysplasia and dentinogenesis imperfecta and also for developing 
therapeutic strategies.
    This material is available for licensing through a PHS Biological 
Materials License.

    Dated: November 13, 2000.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 00-29716 Filed 11-20-00; 8:45 am]
BILLING CODE 4140-01-P


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