Development and metamorphosis in frogs deficient in the thyroid hormone transporter MCT8.

Zachary R Sterner, Ayah Jabrah, Nikko-Ideen Shaidani, Marko E Horb, Rejenae Dockery, Bidisha Paul, Daniel R Buchholz

General and comparative endocrinology 2023 Jan 15

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Precisely regulated thyroid hormone (TH) signaling within tissues during frog metamorphosis gives rise to the organism-wide coordination of developmental events among organs required for survival. This TH signaling is controlled by multiple cellular mechanisms, including TH transport across the plasma membrane. A highly specific TH transporter has been identified, namely monocarboxylate transporter 8 (MCT8), which facilitates uptake and efflux of TH and is differentially and dynamically expressed among tissues during metamorphosis. We hypothesized that loss of MCT8 would alter tissue sensitivity to TH and affect the timing of tissue transformation. To address this, we used CRISPR/Cas9 to introduce frameshift mutations inslc16a2, the gene encoding MCT8, inXenopus laevis. We produced homozygous mutant tadpoles with a 29-bp mutation in the l-chromosome and a 20-bp mutation in the S-chromosome. We found that MCT8 mutants survive metamorphosis with normal growth and development of external morphology throughout the larval period. Consistent with this result, the expression of the pituitary hormone regulating TH plasma levels (tshb) was similar among genotypes as was TH response gene expression in brain at metamorphic climax. Further, delayed initiation of limb outgrowth during natural metamorphosis and reduced hindlimb and tail TH sensitivity were not observed in MCT8 mutants. In sum, we did not observe an effect on TH-dependent development in MCT8 mutants, suggesting compensatory TH transport occurs in tadpole tissues, as seen in most tissues in all model organisms examined. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Zachary R Sterner, Ayah Jabrah, Nikko-Ideen Shaidani, Marko E Horb, Rejenae Dockery, Bidisha Paul, Daniel R Buchholz. Development and metamorphosis in frogs deficient in the thyroid hormone transporter MCT8. General and comparative endocrinology. 2023 Jan 15;331:114179