|
| EXT Mice Model Research |
Osteochondroma / Exostoses Out Line Link (*****You should read these papers, when you would like
to understand MHE / MO / HME research better*****)
The Center for Information Technology (CIT) makes special NIH events, seminars, and lectures available to viewers.
Click this link and view the listing and you can watch these videos
Howard Hughes Medical Institute Holiday Lectures on Science Programs. This four part lecture series held in 2002 will give you a
better insight and understanding of research that is now being conducted in MHE now. Once you have viewed these 4 lectures
you can view other illustrations on this web-page. Click this link
Yu Yamaguchi, Ph.D.
Burnham Institute in La Jolla, California:
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.
These conditional knockout mice, which allow knocking out EXT1 at the site and time of researchers' desire, are very useful for
diverse studies on the function of EXT1/heparan sulfate.
Dr. Yamaguchi and his lab have been able to distribute these mice to more than 20 laboratories around the world (US, Europe,
and Japan) to help studies by other MHE investigators. Using this model system, Dr. Yamaguchi has demonstrated that
mutations of EXT1 influence not only bones but also the nervous system. 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. Dr. Yamaguchi believes these neurological symptoms can be explained by the
deficiency of heparan sulfate in nerve cells. Indeed, recent analysis of knockout mouse behavior has revealed that these mice
have deficits in certain aspects of learning and the levels of fear/anxiety, as well as alterations in nerve cell wiring.
In addition, Dr. Yamaguchi has recently discovered that knockout of EXT1 in stem cells that destined to become bones and
cartilage causes severe bone abnormalities. These findings have provided us with a new insight into the reason why MHE
patients frequently associate a variety of symptoms in addition to exostosis/osteochondroma formation, and suggests potential
novel MHE treatment paradigms.
Jeff Esko, Ph.D.
University of California, San Diego:
“Hereditary multiple exostoses (HME) is a dominant genetic disorder resulting in the formation of generally benign cartilage-
capped tumors in various bones.
Recent work from a number of laboratories indicates that the disease results from mutations in EXT genes involved in making a
complex sugar, or polysaccharide, called heparan sulfate.
Since heparan sulfate interacts with many factors involved in cell growth, this discovery may shed light on the cause of the
disease, which in turn may suggest new treatments.
Studies of HME have relied on analysis of human exostosis samples made available when patients have surgery to remove
problematic growths.
Progress understanding the cause of the disease has been frustrated by the paucity of material available for study and only rare
opportunities to compare the exostosis to normal tissue.
Recently, we discovered that mice bearing mutations in EXT genes also develop exostoses, which mimic many key features of
the human tumors.
One finding that emerged from studies of the HME mice is that the frequency of exostoses is highly variable and depends on
other genetic traits in the mice.
Since we can breed mice rapidly, we are now in a position to identify these other genes that may contribute to the severity of
the disease.
Additionally, we need to work out methods to detect exostoses in live animals, assess treatment strategies for reducing the
frequency and growth of exostoses, and develop systems to look at exostosis development in isolated bones."
Dominique Stickens, Ph.D.
Mice deficient in Ext2 lack heparan sulfate and develop exostoses:
Stickens D, Zak BM, Rougier N, Esko JD, Werb Z.(Dominique Stickens), Department of Anatomy,
University of California, San Francisco, CA 94143-0452, USA.
Hereditary multiple exostoses (HME) is a genetically heterogeneous human disease characterized by the development of bony
outgrowths near the ends of long bones. HME results from mutations in EXT1 and EXT2, genes that encode
glycosyltransferases that synthesize heparan sulfate chains.
To study the relationship of the disease to mutations in these genes, we generated Ext2-null mice by gene targeting.
Homozygous mutant embryos developed normally until embryonic day 6.0, when they became growth arrested and failed to
gastrulate, pointing to the early essential role for heparan sulfate in developing embryos.
Heterozygotes had a normal lifespan and were fertile; however, analysis of their skeletons showed that about one-third of the
animals formed one or more ectopic bone growths (exostoses)
Significantly, all of the mice showed multiple abnormalities in cartilage differentiation, including disorganization of chondrocytes
in long bones and premature hypertrophy in costochondral cartilage.
These changes were not attributable to a defect in hedgehog signaling, suggesting that they arise from deficiencies in other
heparan sulfate-dependent pathways.
The finding that haploinsufficiency triggers abnormal cartilage differentiation gives insight into the complex molecular
mechanisms underlying the development of exostoses.
Dan Wells, Ph.D.
University of Houston:
Multiple Hereditary Exostoses (MHE) is an autosomal dominant skeletal disorder most frequently caused by mutations in the
EXT1 gene.
MHE affects proper development of endochondral bones, such that all affected individuals present with exostoses adjacent to
the growth plate of long bones, while some individuals exhibit additional bone deformities. EXT1 functions as a heparan sulfate
(HS) co-polymerase, and when defective causes improper elongation of glycosaminoglycan side chains on core proteins of HS
proteoglycans.
Although analysis of heterozygous EXT1-deficient mice has failed to reveal any significant gross morphological variations in
skeletal development, significant alterations in molecular signaling occur in the developing long bones.
Our results indicate that defects in EXT1 and the resulting reduction in HS lead to enhanced Indian Hedgehog diffusion causing
an increase in chondrocyte proliferation and delayed hypertrophic differentiation.
Andrea Vortkamp, P.h.D.
Propagation of Ihh signaling:
One important question to understand the IhhP/THrP feedback loop is how the Ihh signal is transported through the growth
plate. In Drosophila the glycosyltransferase ‘tout velu’ (ttv) is necessary to transport the hedgehog signal in the developing
embryo.
Mutations in the human homologues, Ext-1 and Ext-2, result in, Heritable multiple exostoses’ (HME), disease characterized by
benign bone tumors and short stature.In the developing bone we found Ext-1 and Ext-2 both expressed in domains flanking
the Ihh expression domain.
Using transgenic mice and a gene trap line targeting the Ext1 locus we aim to analyze the role of Ext1 during bone devolopment
and to identify a potential function in Ihh transport.
Marion Kuche-Gullberg, Ph.D.
Characterization of enzymes involved in heparan sulfate biosynthesis:
Our area of interest is the structure and function of heparan sulfate (HS). HSs play dynamic functional roles in a diverse
number of biological events related to intracellular signaling, cell-cell interactions and tissue morphogenesis.
HS execute its function by the binding to a variety of molecules including growth factors, serine protease inhibitors and
extracellular matrix proteins.
The biological activities of HS largely depend on the amount and distribution of its sulfate groups that provide specific binding
sites for proteins.
Our overall goal is to understand the mechanisms generating specific saccharide structures and to provide insight into the link
between cell type specific expression of HS modifying enzymes and the biological function of the polysaccharide.
Our research focus on
1. UDP-glucose dehydrogenase, which converts UDP-glucose to UDP-glucuronic acid providing one of the building blocks for
chain elongation
2. heparan sulfate polymerases (EXT1 and EXT2) giving rise to the polysaccharide backbone(mice with a gene trap mutation in
Ext)
3. 2-O- and 6-O-sulfotransferases, incorporating sulfate groups in specific positions, generating biological active heparan
sulfate.
4. Sulfs, cell associated HS 6-O endosulfatases, that remove sulfate groups in specific positions, thus modulating HS
dependent growth factor signaling.
to understand MHE / MO / HME research better*****)
The Center for Information Technology (CIT) makes special NIH events, seminars, and lectures available to viewers.
Click this link and view the listing and you can watch these videos
Howard Hughes Medical Institute Holiday Lectures on Science Programs. This four part lecture series held in 2002 will give you a
better insight and understanding of research that is now being conducted in MHE now. Once you have viewed these 4 lectures
you can view other illustrations on this web-page. Click this link
Yu Yamaguchi, Ph.D.
Burnham Institute in La Jolla, California:
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.
These conditional knockout mice, which allow knocking out EXT1 at the site and time of researchers' desire, are very useful for
diverse studies on the function of EXT1/heparan sulfate.
Dr. Yamaguchi and his lab have been able to distribute these mice to more than 20 laboratories around the world (US, Europe,
and Japan) to help studies by other MHE investigators. Using this model system, Dr. Yamaguchi has demonstrated that
mutations of EXT1 influence not only bones but also the nervous system. 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. Dr. Yamaguchi believes these neurological symptoms can be explained by the
deficiency of heparan sulfate in nerve cells. Indeed, recent analysis of knockout mouse behavior has revealed that these mice
have deficits in certain aspects of learning and the levels of fear/anxiety, as well as alterations in nerve cell wiring.
In addition, Dr. Yamaguchi has recently discovered that knockout of EXT1 in stem cells that destined to become bones and
cartilage causes severe bone abnormalities. These findings have provided us with a new insight into the reason why MHE
patients frequently associate a variety of symptoms in addition to exostosis/osteochondroma formation, and suggests potential
novel MHE treatment paradigms.
Jeff Esko, Ph.D.
University of California, San Diego:
“Hereditary multiple exostoses (HME) is a dominant genetic disorder resulting in the formation of generally benign cartilage-
capped tumors in various bones.
Recent work from a number of laboratories indicates that the disease results from mutations in EXT genes involved in making a
complex sugar, or polysaccharide, called heparan sulfate.
Since heparan sulfate interacts with many factors involved in cell growth, this discovery may shed light on the cause of the
disease, which in turn may suggest new treatments.
Studies of HME have relied on analysis of human exostosis samples made available when patients have surgery to remove
problematic growths.
Progress understanding the cause of the disease has been frustrated by the paucity of material available for study and only rare
opportunities to compare the exostosis to normal tissue.
Recently, we discovered that mice bearing mutations in EXT genes also develop exostoses, which mimic many key features of
the human tumors.
One finding that emerged from studies of the HME mice is that the frequency of exostoses is highly variable and depends on
other genetic traits in the mice.
Since we can breed mice rapidly, we are now in a position to identify these other genes that may contribute to the severity of
the disease.
Additionally, we need to work out methods to detect exostoses in live animals, assess treatment strategies for reducing the
frequency and growth of exostoses, and develop systems to look at exostosis development in isolated bones."
Dominique Stickens, Ph.D.
Mice deficient in Ext2 lack heparan sulfate and develop exostoses:
Stickens D, Zak BM, Rougier N, Esko JD, Werb Z.(Dominique Stickens), Department of Anatomy,
University of California, San Francisco, CA 94143-0452, USA.
Hereditary multiple exostoses (HME) is a genetically heterogeneous human disease characterized by the development of bony
outgrowths near the ends of long bones. HME results from mutations in EXT1 and EXT2, genes that encode
glycosyltransferases that synthesize heparan sulfate chains.
To study the relationship of the disease to mutations in these genes, we generated Ext2-null mice by gene targeting.
Homozygous mutant embryos developed normally until embryonic day 6.0, when they became growth arrested and failed to
gastrulate, pointing to the early essential role for heparan sulfate in developing embryos.
Heterozygotes had a normal lifespan and were fertile; however, analysis of their skeletons showed that about one-third of the
animals formed one or more ectopic bone growths (exostoses)
Significantly, all of the mice showed multiple abnormalities in cartilage differentiation, including disorganization of chondrocytes
in long bones and premature hypertrophy in costochondral cartilage.
These changes were not attributable to a defect in hedgehog signaling, suggesting that they arise from deficiencies in other
heparan sulfate-dependent pathways.
The finding that haploinsufficiency triggers abnormal cartilage differentiation gives insight into the complex molecular
mechanisms underlying the development of exostoses.
Dan Wells, Ph.D.
University of Houston:
Multiple Hereditary Exostoses (MHE) is an autosomal dominant skeletal disorder most frequently caused by mutations in the
EXT1 gene.
MHE affects proper development of endochondral bones, such that all affected individuals present with exostoses adjacent to
the growth plate of long bones, while some individuals exhibit additional bone deformities. EXT1 functions as a heparan sulfate
(HS) co-polymerase, and when defective causes improper elongation of glycosaminoglycan side chains on core proteins of HS
proteoglycans.
Although analysis of heterozygous EXT1-deficient mice has failed to reveal any significant gross morphological variations in
skeletal development, significant alterations in molecular signaling occur in the developing long bones.
Our results indicate that defects in EXT1 and the resulting reduction in HS lead to enhanced Indian Hedgehog diffusion causing
an increase in chondrocyte proliferation and delayed hypertrophic differentiation.
Andrea Vortkamp, P.h.D.
Propagation of Ihh signaling:
One important question to understand the IhhP/THrP feedback loop is how the Ihh signal is transported through the growth
plate. In Drosophila the glycosyltransferase ‘tout velu’ (ttv) is necessary to transport the hedgehog signal in the developing
embryo.
Mutations in the human homologues, Ext-1 and Ext-2, result in, Heritable multiple exostoses’ (HME), disease characterized by
benign bone tumors and short stature.In the developing bone we found Ext-1 and Ext-2 both expressed in domains flanking
the Ihh expression domain.
Using transgenic mice and a gene trap line targeting the Ext1 locus we aim to analyze the role of Ext1 during bone devolopment
and to identify a potential function in Ihh transport.
Marion Kuche-Gullberg, Ph.D.
Characterization of enzymes involved in heparan sulfate biosynthesis:
Our area of interest is the structure and function of heparan sulfate (HS). HSs play dynamic functional roles in a diverse
number of biological events related to intracellular signaling, cell-cell interactions and tissue morphogenesis.
HS execute its function by the binding to a variety of molecules including growth factors, serine protease inhibitors and
extracellular matrix proteins.
The biological activities of HS largely depend on the amount and distribution of its sulfate groups that provide specific binding
sites for proteins.
Our overall goal is to understand the mechanisms generating specific saccharide structures and to provide insight into the link
between cell type specific expression of HS modifying enzymes and the biological function of the polysaccharide.
Our research focus on
1. UDP-glucose dehydrogenase, which converts UDP-glucose to UDP-glucuronic acid providing one of the building blocks for
chain elongation
2. heparan sulfate polymerases (EXT1 and EXT2) giving rise to the polysaccharide backbone(mice with a gene trap mutation in
Ext)
3. 2-O- and 6-O-sulfotransferases, incorporating sulfate groups in specific positions, generating biological active heparan
sulfate.
4. Sulfs, cell associated HS 6-O endosulfatases, that remove sulfate groups in specific positions, thus modulating HS
dependent growth factor signaling.
Heparan Sulfates - Regulators of Cell Functions
Heparan sulfates (HS): are glycans (complex sugars) found on all cell surfaces
which act by binding selectively to a variety of proteins and pathogens and
are critically relevant to many disease processes (eg. , inflammation,
neurodegeneration, angiogenesis, wound healing, cancer, cardiovascular
disordersand infectious diseases). Many of these activities have been detected
using heparin, which is a subclass of the HS family of glycans .
Heparan sulfates (HS): are glycans (complex sugars) found on all cell surfaces
which act by binding selectively to a variety of proteins and pathogens and
are critically relevant to many disease processes (eg. , inflammation,
neurodegeneration, angiogenesis, wound healing, cancer, cardiovascular
disordersand infectious diseases). Many of these activities have been detected
using heparin, which is a subclass of the HS family of glycans .
Heparin and heparan sulphates act by binding to proteins and regulating
their biological activities.
The picture shows the interaction of a small heparin hexasaccharide (6 sugar
units) with the growth factor called basic FGF that controls the growth and
differentiation of many cell types.
The HS family of sugars are composed of long chains of repeating disaccharide
units of uronic acid and glucosamine residues, decorated by variable patterns of
sulphate and carboxyl groups, giving them very strong negative charge.
They are produced in living cells by a complex multi-step enzymatic biosynthetic
process.
Heparin is a highly sulphated and relatively structurally homogenous molecule
compared to cellular heparan sulphates, which have increased sequence
diversity and fulfil many complex biological functions by interacting with
proteins and influencing their biological activities.
units of uronic acid and glucosamine residues, decorated by variable patterns of
sulphate and carboxyl groups, giving them very strong negative charge.
They are produced in living cells by a complex multi-step enzymatic biosynthetic
process.
Heparin is a highly sulphated and relatively structurally homogenous molecule
compared to cellular heparan sulphates, which have increased sequence
diversity and fulfil many complex biological functions by interacting with
proteins and influencing their biological activities.
Animated picture shows an extended helical
heparin sequence with sulphate groups
(yellow/red) decorating the backbone (image
courtesy of Dr Barbara Mulloy, National
Institiute of Biological Standards, Herts, UK)
heparin sequence with sulphate groups
(yellow/red) decorating the backbone (image
courtesy of Dr Barbara Mulloy, National
Institiute of Biological Standards, Herts, UK)
HS/heparin structure
HS and heparin are long, linear chains of sugars, composed of repeating
disaccharide units made up of alternating uronic acid (glucuronic or iduronic
acid) and glucosamine residues. The backbone structure is then decorated
with complex patterns of sulphate groups at various positions.
HS and heparin are long, linear chains of sugars, composed of repeating
disaccharide units made up of alternating uronic acid (glucuronic or iduronic
acid) and glucosamine residues. The backbone structure is then decorated
with complex patterns of sulphate groups at various positions.
HS and heparin are produced on cells by a complex process involving the
sequential action of multiple enzymes which knit together the repeating
disaccharide units (polymerases) and then modify them with exquisitely
complex patterns of sulphate groups (sulfotransferases). The resulting
structural motifs bind to specific proteins and influence their biological
activities.
sequential action of multiple enzymes which knit together the repeating
disaccharide units (polymerases) and then modify them with exquisitely
complex patterns of sulphate groups (sulfotransferases). The resulting
structural motifs bind to specific proteins and influence their biological
activities.
Heparan sulphate binds proteins
Heparin and heparan sulphates act by binding to proteins and regulating their
biological activities.
The picture shows the interaction of a small heparin hexasaccharide (6 sugar
units) with the growth factor called basic FGF that controls the growth and
differentiation of many cell types.
Heparin and heparan sulphates act by binding to proteins and regulating their
biological activities.
The picture shows the interaction of a small heparin hexasaccharide (6 sugar
units) with the growth factor called basic FGF that controls the growth and
differentiation of many cell types.
|
heparan sulfate proteoglycans (HSPGs), are ubiquitous glycoproteins present at the cell surface and in the extracellular matrix,
and have their roles in neuron migration, process outgrowth and guidance and in synapse formation. HSPGs contain a protein
core substituted with heparan sulphate (HS) polysaccharide chains, which encode complex sugar sequences with variant
sulfation patterns that confer biological functions as protein regulators. HS/HSPGs play essential roles in controlling cell
differentiation, tissue morphogenesis and homeostasis. In the nervous system, HS and HSPGs have been implicated in neuron
migration, axon guidance, synapse formation and maturation and control of physiological responses such as feeding, learning
and memory.
and have their roles in neuron migration, process outgrowth and guidance and in synapse formation. HSPGs contain a protein
core substituted with heparan sulphate (HS) polysaccharide chains, which encode complex sugar sequences with variant
sulfation patterns that confer biological functions as protein regulators. HS/HSPGs play essential roles in controlling cell
differentiation, tissue morphogenesis and homeostasis. In the nervous system, HS and HSPGs have been implicated in neuron
migration, axon guidance, synapse formation and maturation and control of physiological responses such as feeding, learning
and memory.
| What is a chondrocyte |
Chondrocytes (from Greek chondros cartilage + kytos cell) are the only cells found in cartilage. They produce and maintain the
cartilaginous matrix, which consists mainly of collagen and proteoglycans.
To view a short video of what is chondrocyte is please click the tab
cartilaginous matrix, which consists mainly of collagen and proteoglycans.
To view a short video of what is chondrocyte is please click the tab
Slide: Jeffrey D Esko, Phd
Joseph R. Bishop, Manuela Schuksz, Jeffrey D. Esko
Heparan sulphate proteoglycans reside on the plasma membrane of all animal cells studied so far and are a major component of
extracellular matrices. Studies of model organisms and human diseases have demonstrated their importance in development
and normal physiology. A recurrent theme is the electrostatic interaction of the heparan sulphate chains with protein ligands,
which affects metabolism, transport, information transfer, support and regulation in all organ systems. The importance of these
interactions is exemplified by phenotypic studies of mice and humans bearing mutations in the core proteins or the biosynthetic
enzymes responsible for assembling the heparan sulphate chains.
SUMMARY: Heparan sulphate proteoglycans reside on the plasma membrane of all animal cells studied so far and are a major
component of extracellular matrices. Studies of model organisms and human diseases
CONTEXT: hereditary multiple exostoses, an autosomal dominant disease characterized by the formation of cartilage-capped
bony outgrowths (osteochondromas or exostoses) on growth plates throughout the body. Heterozygous mice also develop...
Nature 446, 1030 - 1037 (25 Apr 2007) Insight
Heparan sulphate proteoglycans reside on the plasma membrane of all animal cells studied so far and are a major component of
extracellular matrices. Studies of model organisms and human diseases have demonstrated their importance in development
and normal physiology. A recurrent theme is the electrostatic interaction of the heparan sulphate chains with protein ligands,
which affects metabolism, transport, information transfer, support and regulation in all organ systems. The importance of these
interactions is exemplified by phenotypic studies of mice and humans bearing mutations in the core proteins or the biosynthetic
enzymes responsible for assembling the heparan sulphate chains.
SUMMARY: Heparan sulphate proteoglycans reside on the plasma membrane of all animal cells studied so far and are a major
component of extracellular matrices. Studies of model organisms and human diseases
CONTEXT: hereditary multiple exostoses, an autosomal dominant disease characterized by the formation of cartilage-capped
bony outgrowths (osteochondromas or exostoses) on growth plates throughout the body. Heterozygous mice also develop...
Nature 446, 1030 - 1037 (25 Apr 2007) Insight
|
For more detailed information concerning the Perichondrium, chondrocytes, PTHrP, Ihh and other signaling
pathways affected by the defect in the EXT genes please view the video.
April 25–28, 2007, the 2nd Conference on Skeletal Biology and Medicine held in NYC.
This meeting, was jointly hosted at the New York Academy of Sciences and Mount Sinai School of Medicine, was
organized and chaired by Mone Zaidi, professor of endocrinology, geriatrics and adult development, and structural and chemical
biology at Mount Sinai. Cochairs were Gerard Karsenty of Columbia University and Steven Teitelbaum of the Washington
University School of Medicine.
The MHE Research would like to thank all for the use of the presentation on the MHE Research Foundation website.
To view this video presentation given by Dr. Henry Kronenberg during this conference please click the link tab
pathways affected by the defect in the EXT genes please view the video.
April 25–28, 2007, the 2nd Conference on Skeletal Biology and Medicine held in NYC.
This meeting, was jointly hosted at the New York Academy of Sciences and Mount Sinai School of Medicine, was
organized and chaired by Mone Zaidi, professor of endocrinology, geriatrics and adult development, and structural and chemical
biology at Mount Sinai. Cochairs were Gerard Karsenty of Columbia University and Steven Teitelbaum of the Washington
University School of Medicine.
The MHE Research would like to thank all for the use of the presentation on the MHE Research Foundation website.
To view this video presentation given by Dr. Henry Kronenberg during this conference please click the link tab
| Jeffrey D Esko, Ph.D. "What is MHE Research" Click Here to view this video presentation |
This presentation will open in a new browser window
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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
The MHE Research Foundation is proud to be working with the EuroBoNeT consortium, a European Commission granted Network of Excellence for
studying the pathology and genetics of bone tumors.
studying the pathology and genetics of bone tumors.
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Disclaimer: While many find the information useful, it is in no way a substitute for professional medical care. The information provided here is for educational
and informational purposes only. This website does not engage in the practice of medicine. In all cases we recommend that you consult your own physician
regarding any course of treatment or medicine.
and informational purposes only. This website does not engage in the practice of medicine. In all cases we recommend that you consult your own physician
regarding any course of treatment or medicine.
The MHE Research Foundation is proud to be an affiliate of the Society For Glycobiology
