Deleting Cellular Retinoic-Acid-Binding Protein-1 (Crabp1) Gene Causes Adult-Onset Primary Hypothyroidism in Mice

Fatimah Najjar, Jennifer Nhieu, Chin-Wen Wei, Liming Milbauer, Lynn A Burmeister, Davis Seelig, Li-Na Wei

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Adult-onset primary hypothyroidism is commonly caused by iatrogenic or autoimmune mechanisms; whether other factors might also contribute to adult hypothyroidism is unclear. Cellular Retinoic-Acid-Binding Protein 1 (CRABP1) is a mediator for Non-canonical signalling of all-trans retinoic acid (atRA). CRABP1 Knockout (CKO) mice develop and reproduce normally but begin to exhibit primary hypothyroidism in adults (~3 months old) including increased body weight, decreased body temperature, reduced plasma levels of triiodothyronine and thyroxine, and elevated levels of thyroid-stimulating hormone. Histopathological and gene expression studies reveal significant thyroid gland morphological abnormalities and altered expression of genes involved in thyroid hormone synthesis, transport, and metabolism in the CKO thyroid gland at ~6 months old. These significantly affected genes in CKO mice are also found to be genetically altered in human patients with hypothyroidism which could result in a loss of function, supporting the clinical relevance of CKO mice in humans with hypothyroidism. This study identifies, for the first time, an important role for CRABP1 in maintaining the health of the thyroid gland in adults and reports that CKO mice may provide an experimental animal model for studying the mechanisms underlying the development of adult hypothyroidism in humans.

Original languageEnglish (US)
Pages (from-to)138-150
Number of pages13
JournalEndocrines
Volume4
Issue number1
DOIs
StatePublished - Mar 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • CRABP1
  • hypothyroidism
  • retinoic acid
  • thyroid gland
  • thyroid hormones
  • vitamin A

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