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Phenotypes of conditional Ext1 knockout mice:
Insights into non-skeletal symptoms of MHE
Abstract 2005 MHE Conference
Yu Yamaguchi, M.D., Ph.D.
Developmental Neurobiology Program The Burnham Institute, La Jolla, CA 92037
Heparan sulfate proteoglycans have been implicated in various cell biological and developmental
processes, such as growth factor and morphogen signaling, cell adhesion and migration, and
extracellular matrix assembly.
To study the physiological roles of heparan sulfate proteoglycans in the mammalian development, we
created conditional allele of Ext1, the gene encoding a glycosyltransferase required for heparan
sulfate biosynthesis.
Mice carrying this allele have been crossed with several Cre transgenic mice to determine the function
of heparan sulfate in different embryonic and adult tissues. I will present our recent findings on the
phenotypes of these conditional knockout mice, and discuss molecular mechanisms underlying such
phenotypes and potential implications into non-skeletal symptoms of MHE.
My laboratory has been studying the role of EXT1/heparan sulfate in mouse embryonic
development. We have created a conditional EXT1 knockout mouse model. These conditional EXT1
knockout mice are being used for genetic studies to figure out how the deficiency of EXT1/heparan
sulfate causes MHE.
Our conditional knockout mice, which allow knocking out EXT1 at the site and time of researchers'
desire, they are very useful for diverse studies on the function of EXT1/heparan sulfate. Our mice
have already been distributed to more than a dozen laboratories in the world (US, Europe, and
Japan) to help studies by other MHE investigators. Meanwhile, the main focus of my laboratory is
the brain, nerves, and muscles.
Through an informal survey conducted by Sarah Ziegler, we have realized that, although frequently
ignored in the clinical front, MHE patients tend to have some mental, neurological, and muscular
symptoms. Such symptoms include: mild social interaction deficits (excessive shyness, adherence to
routines), heightened sensitivities to sensory stimulation (sounds, touch, taste), difficulties to
concentrate, and muscle weakness (easy to get tired) and pain.
We believe these symptoms can be explained by the deficiency of heparan sulfate in nerve and
muscle cells. Indeed, our recent analysis of knockout mouse behavior has suggested that these
mice have deficits in social interaction and reduced levels of fear/anxiety.
In addition, we have recently discovered that knockout of EXT1 in the “neural crest cell” (which is a
cell type that develops into various bones as well as nerves), causes skeletal defects. This finding
has provided us with a new insight into the reason why “exostosis” develops in MHE patient and into
potential MHE treatment paradigm.
Insights into non-skeletal symptoms of MHE
Abstract 2005 MHE Conference
Yu Yamaguchi, M.D., Ph.D.
Developmental Neurobiology Program The Burnham Institute, La Jolla, CA 92037
Heparan sulfate proteoglycans have been implicated in various cell biological and developmental
processes, such as growth factor and morphogen signaling, cell adhesion and migration, and
extracellular matrix assembly.
To study the physiological roles of heparan sulfate proteoglycans in the mammalian development, we
created conditional allele of Ext1, the gene encoding a glycosyltransferase required for heparan
sulfate biosynthesis.
Mice carrying this allele have been crossed with several Cre transgenic mice to determine the function
of heparan sulfate in different embryonic and adult tissues. I will present our recent findings on the
phenotypes of these conditional knockout mice, and discuss molecular mechanisms underlying such
phenotypes and potential implications into non-skeletal symptoms of MHE.
My laboratory has been studying the role of EXT1/heparan sulfate in mouse embryonic
development. We have created a conditional EXT1 knockout mouse model. These conditional EXT1
knockout mice are being used for genetic studies to figure out how the deficiency of EXT1/heparan
sulfate causes MHE.
Our conditional knockout mice, which allow knocking out EXT1 at the site and time of researchers'
desire, they are very useful for diverse studies on the function of EXT1/heparan sulfate. Our mice
have already been distributed to more than a dozen laboratories in the world (US, Europe, and
Japan) to help studies by other MHE investigators. Meanwhile, the main focus of my laboratory is
the brain, nerves, and muscles.
Through an informal survey conducted by Sarah Ziegler, we have realized that, although frequently
ignored in the clinical front, MHE patients tend to have some mental, neurological, and muscular
symptoms. Such symptoms include: mild social interaction deficits (excessive shyness, adherence to
routines), heightened sensitivities to sensory stimulation (sounds, touch, taste), difficulties to
concentrate, and muscle weakness (easy to get tired) and pain.
We believe these symptoms can be explained by the deficiency of heparan sulfate in nerve and
muscle cells. Indeed, our recent analysis of knockout mouse behavior has suggested that these
mice have deficits in social interaction and reduced levels of fear/anxiety.
In addition, we have recently discovered that knockout of EXT1 in the “neural crest cell” (which is a
cell type that develops into various bones as well as nerves), causes skeletal defects. This finding
has provided us with a new insight into the reason why “exostosis” develops in MHE patient and into
potential MHE treatment paradigm.
Dr. Yamaguchi serves on the Scientific and Medical Advisory Board of the MHE Research Foundation
Research authored by Dr. Yamaguchi
Click the tab and a window will appear.
List of Publications via PubMed
(NIH National Library of Medicine)
Research authored by Dr. Yamaguchi
Click the tab and a window will appear.
List of Publications via PubMed
(NIH National Library of Medicine)
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Dr. Yamaguchi's research
| On September 30, 2007 during the FUNTASIA Research banquet Dr. Yamaguchi was presented with the "The Humanitarian Scientific Achievement Award" along with CITATION from Borough of Brooklyn City of New York, Office of the President, Presented by the President Marty Markowitz. PROCLAMATION from New York State Senate, Presented by Senator Martin J. Golden. CERTIFICATE OF RECOGNITION in honor of their Commitment to the MHE Research Foundation from United States Congress U.S. House of Representatives, Presented by Congressman Vito J. Fossella. To read more about this event Click Here |
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By the Health On the Net Foundation. Click here to verify.# HON Conduct 282463 and is linked on the NIH
National Library of Medicine, Directory of Health Organizations (SIS) website, as well as the link for Patient
Information on The Diseases Database a cross-referenced index of human disease, and the Intute: health & life
sciences a free online service providing access to the very best Web resources for education and research
located in the UK
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Press Release 5/ 09 / 08
We are pleased to announce Yu Yamaguchi, M.D., PH.D. has been named as one of the three senor
investigators at the new Sanford Children’s Health Research Center located at the Burnham Institute
for Medical Research in San Diego CA, where he will continue his research efforts to read this Press
Release Click Here
We are pleased to announce Yu Yamaguchi, M.D., PH.D. has been named as one of the three senor
investigators at the new Sanford Children’s Health Research Center located at the Burnham Institute
for Medical Research in San Diego CA, where he will continue his research efforts to read this Press
Release Click Here