New Mouse Model May Provide Insights Into Rare Genetic Syndrome

By September 22, 2012 August 8th, 2017 2012 News Releases, 82nd Annual Meeting News, News Releases

Falls Church, Virginia. Sep. 22, 2012—New mouse models can help scientists study a rare disease, called SECISBP2 syndrome, that causes abnormal thyroid hormone metabolism, delayed bone maturation, as well as other abnormal characteristics that vary by individual, according to new data presented at the 82nd Annual Meeting of the American Thyroid Association (ATA) in Québec City, Québec, Canada.

“SECISBP2 syndrome has confounded the scientific community. New approaches to study the biological underpinnings of SECISBP2 syndrome are thus critical to truly make progress against this disorder,” said Douglas Forrest, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases, and Program Co-Chair of the ATA Annual Meeting.

SECISBP2 syndrome is caused by an atypical resistance to thyroid hormone In patients with this disease, aberrant thyroid hormone levels (high T4, low T3, elevated rT3, and high-to-normal TSH) indicate a defect in deiodinase-dependent thyroid hormone metabolism. Findings of reduced concentrations of plasma selenoproteins suggested a generalized defect of selenoprotein biosynthesis and led to the identification of mutations in the SECISBP2 gene. SECISBP2 is thought to play an essential role for selenoprotein biosynthesis. Mutations in the SECISBP2 gene lead to reduced expression of selenoproteins and cause a syndrome with relatively mild to more severe phenotypes.

A team of researchers led by Sandra Seeher at the Institut für Experimentelle Endokrinologie, Charité – Universitätsmedizin Berlin in Berlin, Germany, set out to create mouse models to test whether Secisbp2 is essential for selenoprotein biosynthesis and to study the consequences of Secisbp2 deletion in tissues and the whole organism.
Researchers found that the necessity of Secisbp2, using a constitutional knockout, leads to early embryonic lethality. Nevertheless, Secisbp2 heterozygotes have no obvious phenotype; they are fertile, and their thyroid function tests are normal. Biochemical analysis revealed only minimal changes in selenoprotein expression. Hepatocyte-specific Secisbp2 knockout mice also appear normal, but show a dramatic reduction of hepatic selenoprotein expression. Neuron-specific Secisbp2 knockout mice have a more severe phenotype and survive for approximately three weeks. They are smaller and weigh less than their wild-type littermates, and exhibit a marked movement phenotype with an awkward, broad based, and dystonic gait.

Immunohistochemical stainings demonstrated a specific loss of parvalbumin-positive interneurons in somatosensory cortex and hippocampus. Researchers then compared Secisbp2 mice with similar mouse models lacking tRNA[Ser]Sec. They found that the phenotypes, as well as the consequences on selenoprotein level of our Secisbp2 mice are milder than in tRNA[Ser]Sec knockout mice. Research therefore intend to alternative factors that could compensate for Secisbp2 function.

About the ATA Annual Meeting 

The 82nd Annual Meeting of the American Thyroid Association is held Sept.19-23, in Québec City, Québec, Canada. This four-day creative and innovative scientific program, chaired by Elizabeth Pearce, MD, Boston Medical Center, and Douglas Forrest, PhD, National Institute of Diabetes and Digestive and Kidney Diseases, carefully balances clinical and basic science sessions on the latest advances in thyroidology. The ATA meeting is designed to offer continuing education for endocrinologists, internists, surgeons, basic scientists, nuclear medicine scientists, pathologists, endocrine fellows and nurses, physician assistants and other health care professionals. Visit for more information.

About the ATA 

The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis and treatment of thyroid disorders and thyroid cancer. ATA is an international individual membership organization with over 1,600 members from 43 countries around the world. Celebrating its 89th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, THYROID, Clinical Thyroidology and Clinical Thyroidology for Patients; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators, support of online professional, public and patient educational programs through; and the development of guidelines for clinical management of thyroid disease. Visit for more information.

Media Contact
Bobbi Smith
Executive Director
 of the American Thyroid Association

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