Sandra M. McLachlan
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View article: The NOD Mouse Beyond Autoimmune Diabetes
The NOD Mouse Beyond Autoimmune Diabetes Open
Autoimmune diabetes arises spontaneously in Non-Obese Diabetic (NOD) mice, and the pathophysiology of this disease shares many similarities with human type 1 diabetes. Since its generation in 1980, the NOD mouse, derived from the Cataract …
View article: Insulin-like Growth Factor 1 and Prolactin Levels in Chimpanzees (Pan troglodytes) Across the Lifespan
Insulin-like Growth Factor 1 and Prolactin Levels in Chimpanzees (Pan troglodytes) Across the Lifespan Open
As human and chimpanzee genomes show high homology for IGF1 and PRL, we analyzed the sera of 367 healthy chimpanzees obtained during routine physical examinations in a single colony and measured chimpanzee insulin-like growth factor (IGF)-…
View article: Meeting Program and Abstracts
Meeting Program and Abstracts Open
The non recurrent laryngeal nerve (NRN) is an anatomical abnormality
\nthat, altrhought rare (0,03-1% on the right, only 4 cases on the
\nleft), represents a serious threat of recurrent lesioni during thyroidectomy.
\nThe existence of anat…
View article: A Mouse Thyrotropin Receptor A-Subunit Transgene Expressed in Thyroiditis-Prone Mice May Provide Insight into Why Graves' Disease Only Occurs in Humans
A Mouse Thyrotropin Receptor A-Subunit Transgene Expressed in Thyroiditis-Prone Mice May Provide Insight into Why Graves' Disease Only Occurs in Humans Open
Background: Graves' disease, caused by autoantibodies that activate the thyrotropin (TSH) receptor (TSHR), has only been reported in humans. Thyroiditis-prone NOD.H2h4 mice develop autoantibodies to thyroglobulin (Tg) and thyroid peroxidas…
View article: Nanoparticles Bearing TSH Receptor Protein and a Tolerogenic Molecule Do Not Induce Immune Tolerance but Exacerbate Thyroid Autoimmunity in hTSHR/NOD.<i>H2h4</i> Mice
Nanoparticles Bearing TSH Receptor Protein and a Tolerogenic Molecule Do Not Induce Immune Tolerance but Exacerbate Thyroid Autoimmunity in hTSHR/NOD.<i>H2h4</i> Mice Open
Transgenic NOD.H2h4 mice that express the human (h) TSHR A-subunit in the thyroid gland spontaneously develop pathogenic TSHR autoantibodies resembling those in patients with Graves disease. Nanoparticles coupled to recombinant hTSHR A-sub…
View article: To reflect human autoimmune thyroiditis, thyroid peroxidase (not thyroglobulin) antibodies should be measured in female (not sex-independent) NOD.<i>H2h4</i> mice
To reflect human autoimmune thyroiditis, thyroid peroxidase (not thyroglobulin) antibodies should be measured in female (not sex-independent) NOD.<i>H2h4</i> mice Open
Summary NOD.H2h4 mice are the most commonly used model for human autoimmune thyroiditis. Because thyroid autoimmunity develops slowly (over months), NOD.H2h4 mice are usually exposed to excess dietary iodide to accelerate and amplify the p…
View article: Reflections on Thyroid Autoimmunity: A Personal Overview from the Past into the Future
Reflections on Thyroid Autoimmunity: A Personal Overview from the Past into the Future Open
After investigating thyroid autoimmunity for more than 40 years, we present a personal perspective on the field. Despite effective therapies for Graves’ hyperthyroidism and Hashimoto’s thyroiditis, cures are elusive. Novel forms of therapy…
View article: Structure of a Thyrotropin Receptor Monoclonal Antibody Variable Region Provides Insight into Potential Mechanisms for its Inverse Agonist Activity
Structure of a Thyrotropin Receptor Monoclonal Antibody Variable Region Provides Insight into Potential Mechanisms for its Inverse Agonist Activity Open
Structural insight at atomic resolution of a TSHR antibody with inverse agonist activity opens the way for the development of a molecule with therapeutic potential, particularly in thyroid carcinoma. For this purpose, CS-17 will require "h…
View article: Supplementary Material for: Thyroid Hemiagenesis in a Thyroiditis Prone Mouse Strain
Supplementary Material for: Thyroid Hemiagenesis in a Thyroiditis Prone Mouse Strain Open
Background: Thyroid hemiagenesis, a rare congenital condition detected by ultrasound screening of the neck, is usually not manifested clinically in humans. This condition has been reported in mice with hypothyroidism associated with induce…
View article: Thyroid Hemiagenesis in a Thyroiditis Prone Mouse Strain
Thyroid Hemiagenesis in a Thyroiditis Prone Mouse Strain Open
Unlike hypothyroidism associated with hemiagenesis in transcription factor knockout mice, hemiagenesis in euthyroid NOD.H2h4 mice occurs spontaneously and is phenotypically similar to that occasionally observed in humans.
View article: Thyroid Autoantibodies Display both “Original Antigenic Sin” and Epitope Spreading
Thyroid Autoantibodies Display both “Original Antigenic Sin” and Epitope Spreading Open
Evidence for original antigenic sin in spontaneous thyroid autoimmunity is revealed by autoantibody interactions with immunodominant regions on thyroid autoantigens, thyroglobulin (Tg), thyroid peroxidase (TPO), and the thyrotropin recepto…
View article: Aberrant Iodine Autoregulation Induces Hypothyroidism in a Mouse Strain in the Absence of Thyroid Autoimmunity
Aberrant Iodine Autoregulation Induces Hypothyroidism in a Mouse Strain in the Absence of Thyroid Autoimmunity Open
We investigated factors underlying the varying effects of a high dietary iodide intake on serum T4 levels in a wide spectrum of mouse strains, including thyroiditis-susceptible NOD.H2h4, NOD.H2k, and NOD mice, as well as other strains (BAL…
View article: Variable Effects of Dietary Selenium in Mice That Spontaneously Develop a Spectrum of Thyroid Autoantibodies
Variable Effects of Dietary Selenium in Mice That Spontaneously Develop a Spectrum of Thyroid Autoantibodies Open
Selenium (Se) is a critical element in thyroid function, and variable dietary Se intake influences immunity. Consequently, dietary Se could influence development of thyroid autoimmunity and provide an adjunct to treat autoimmune thyroid dy…
View article: Mechanisms of Autoantibody-Induced Pathology
Mechanisms of Autoantibody-Induced Pathology Open
Autoantibodies are frequently observed in healthy individuals. In a minority of these individuals, they lead to manifestation of autoimmune diseases, such as rheumatoid arthritis or Gravesâ disease. Overall, more than 2.5% of the populat…
View article: High-level intrathymic thyrotrophin receptor expression in thyroiditis-prone mice protects against the spontaneous generation of pathogenic thyrotrophin receptor autoantibodies
High-level intrathymic thyrotrophin receptor expression in thyroiditis-prone mice protects against the spontaneous generation of pathogenic thyrotrophin receptor autoantibodies Open
Summary The thyrotrophin receptor (TSHR) A-subunit is the autoantigen targeted by pathogenic autoantibodies that cause Graves' hyperthyroidism, a common autoimmune disease in humans. Previously, we reported that pathogenic TSHR antibodies …
View article: Genes Outside the Major Histocompatibility Complex Locus Are Linked to the Development of Thyroid Autoantibodies and Thyroiditis in NOD.H2h4 Mice
Genes Outside the Major Histocompatibility Complex Locus Are Linked to the Development of Thyroid Autoantibodies and Thyroiditis in NOD.H2h4 Mice Open
Thyroiditis and autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) develop spontaneously in NOD.H2h4 mice, a phenotype enhanced by dietary iodine. NOD.H2h4 mice were derived by introducing the major histocompatibility cl…
View article: Critical Differences between Induced and Spontaneous Mouse Models of Graves’ Disease with Implications for Antigen-Specific Immunotherapy in Humans
Critical Differences between Induced and Spontaneous Mouse Models of Graves’ Disease with Implications for Antigen-Specific Immunotherapy in Humans Open
Graves’ hyperthyroidism, a common autoimmune disease caused by pathogenic autoantibodies to the thyrotropin (TSH) receptor (TSHR), can be treated but not cured. This single autoantigenic target makes Graves’ disease a prime candidate for A…
View article: TSH Receptor Cleavage Into Subunits and Shedding of the A-Subunit; A Molecular and Clinical Perspective
TSH Receptor Cleavage Into Subunits and Shedding of the A-Subunit; A Molecular and Clinical Perspective Open
The TSH receptor (TSHR) on the surface of thyrocytes is unique among the glycoprotein hormone receptors in comprising two subunits: an extracellular A-subunit, and a largely transmembrane and cytosolic B-subunit. Unlike its ligand TSH, who…