ESPE Abstracts (2021) 94 P1-193

1INSERM U1016, Cochin Institute, Université de Paris, Paris, France; 2IMAGINE Institute, Paris, France; 3Pediatric Endocrinology, Gynecology and Diabetology Unit, Hôpital Universitaire Necker-Enfants Malades, AP-HP, Paris, France; 4Bioinformatics Platform, IMAGINE Institute, Université de Paris, Paris, France; 5Department of Obstetrics and Gynecology, University Hospitals Paris Nord Val de Seine (HUPNVS), AP-HP, Bichat Hospital, Paris, France; 6Centre de Référence des Maladies Endocriniennes Rares de la Croissance et du Développement, Necker-Enfants Malades University Hospital, Paris, France; 7Centre Régional de Dépistage Néonatal (CRDN) Ile de France, Paris, France

Background: We found BOREALIN/CDCA8 mutations in patients with Congenital Hypothyroidism and Thyroid Dysgenesis, varying from asymmetric lobes to athyreosis (Carré et al. Hum Mol Genet 2017). Borealin is a major component of the Chromosomal Passenger Complex, an essential regulator of mitosis. We demonstrated a new feature of BOREALIN: involvement in the adhesion and the migration of the thyrocytes.

Objective: Further understand the role of Borealin in thyroid development and function.

Methods: Borealin+/- mice were studied during development, at the adult stage and during old age. Borealin-/- mice were not available because they die at E5.5. We documented thyroid morphology, performed immunohistology with thyroid markers (Nkx2-1, Thyroglobulin, T4) and we analyzed the thyroid function. We used a well-established model with antithyroid drug induced hypothyroidism which was applied to the Borealin+/- and wild-type mice.

Results: First of all, Borealin+/- mice had no hypothyroidism at the adult stage (4-month-old) but they were significantly more sensitive with a more profound hypothyroidism than wild-type when treated with antithyroid drugs (T4: 41% less for Borealin+/-vs wild-type, P < 0.01). Thyroids of Borealin +/- mice were significantly hyperplastic with larger follicles surfaces in comparison with wild-type (P < 0.05). Thus, the Borealin+/- mice remain euthyroid because they developed a goiter. For elder mice, thyroid morphology of Borealin+/- was altered with heterogeneity in size of follicles with predominantly very large follicles and thyroids that were significantly hyperplastic compared with wild-type (0,34mg/g thyroid weight/animal weight vs 0,23mg/g, P < 0.05). We found that thyroids of Borealin+/- were significantly hyperplastic at E9.5 in comparison with wild-type, and hypoplastic from E11.5 to E17.5 (P < 0.05). Thyroid development thus was abnormal in Borealin+/- compared to wild-type.

Summary: Thyroid development is altered in Borealin+/- mice. Goiter do develop in adult Borealin+/- mice and they are more prone to hypothyroidism when treated with anti-thyroid drugs.

Conclusion: Borealin is involved during crucial steps of the thyroid lifetime cycle. These data demonstrated the involvement of Borealin in the structural organization of the thyroid gland. The role of Borealin in thyroid development and function was strengthened here and supports its involvement in thyroid dysgenesis of patients with congenital hypothyroidism.

Supported in part by Sandoz SAS, Merck, INSERM (new researcher grant)

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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