Медицинская библиотека · Molecular metabolism · 2022

Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome.

Maity-Kumar Gandhari, Ständer Lisa, DeAngelis Meri, Lee Sooyeon, Molenaar Anna, Becker Lore, Garrett Lillian, Amerie Oana V, Hoelter Sabine M, Wurst Wolfgang, Fuchs Helmut, Feuchtinger Annette, Gailus-Durner Valerie, Garcia-Caceres Cristina, Othman Ahmed E, Brockmann Caroline, Schöffling Vanessa I, Beiser Katja, Krude Heiko, Mroz Piotr A, Hofmann Susanna, Tuckermann Jan, DiMarchi Richard D, Hrabe de Angelis Martin, Tschöp Matthias H, Pfluger Paul T, Müller Timo D

СтатьяПоддержка исследования: вне правительства СШАПеревод пока не подготовлен

Аннотация

OBJECTIVE

The Allan-Herndon-Dudley syndrome (AHDS) is a severe disease caused by dysfunctional central thyroid hormone transport due to functional loss of the monocarboxylate transporter 8 (MCT8). In this study, we assessed whether mice with concomitant deletion of the thyroid hormone transporters Mct8 and the organic anion transporting polypeptide (Oatp1c1) represent a valid preclinical model organism for the AHDS.

METHODS

We generated and metabolically characterized a new CRISPR/Cas9 generated Mct8/Oatp1c1 double-knockout (dKO) mouse line for the clinical features observed in patients with AHDS.

RESULTS

We show that Mct8/Oatp1c1 dKO mice mimic key hallmarks of the AHDS, including decreased life expectancy, central hypothyroidism, peripheral hyperthyroidism, impaired neuronal myelination, impaired motor abilities and enhanced peripheral thyroid hormone action in the liver, adipose tissue, skeletal muscle and bone.

CONCLUSIONS

We conclude that Mct8/Oatp1c1 dKO mice are a valuable model organism for the preclinical evaluation of drugs designed to treat the AHDS.

Для цитирования: Maity-Kumar Gandhari, Ständer Lisa, DeAngelis Meri, Lee Sooyeon, Molenaar Anna, Becker Lore, Garrett Lillian, Amerie Oana V, Hoelter Sabine M, Wurst Wolfgang, Fuchs Helmut, Feuchtinger Annette, Gailus-Durner Valerie, Garcia-Caceres Cristina, Othman Ahmed E, Brockmann Caroline, Schöffling Vanessa I, Beiser Katja, Krude Heiko, Mroz Piotr A, Hofmann Susanna, Tuckermann Jan, DiMarchi Richard D, Hrabe de Angelis Martin, Tschöp Matthias H, Pfluger Paul T, Müller Timo D. Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome.. Molecular metabolism. 2022. DOI: 10.1016/j.molmet.2022.101616.

Предметные рубрики MeSH

Animals Mice Monocarboxylic Acid Transporters Symporters X-Linked Intellectual Disability Thyroid Hormones Muscle Hypotonia Muscular Atrophy

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