Generation and Characterization of a New Resistance to Thyroid Hormone Mouse Model with Thyroid Hormone Receptor Alpha Gene Mutation

Liang, Yue; Zhao, Defa; Wang, Ranran; Dang, Pingping; Xi, Yue; Zhang, Dan; Wang, Wei; Shan, Zhongyan; Teng, Xiaochun; Wang, Teng

doi:10.1089/thy.2019.0733

Cited by 5 publications

(4 citation statements)

References 42 publications

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“… 10 , 11 Each subtype has different isoforms, such as THRα1, THRα2, THRβ1, THRβ2 and THRβ3. 10 , 12 These receptors possess specific organ distribution characteristics. 8 , 11 Additionally, genetic defects involving TH cell transport and metabolism have been reported, broadening the understanding of impaired TH sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Thyroid hormone resistance syndrome due to a novel heterozygous mutation and concomitant Hashimoto’s Thyroiditis: A pedigree report

Xie

et al. 2022

J Int Med Res

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Thyroid hormone resistance syndrome (THRS) is a rare disease characterized by reduced sensitivity to thyroid hormones. Mutations in the thyroid hormone receptor beta ( THRB) gene are considered as contributing to the pathogenesis. This report describes a Chinese pedigree with THRS and Hashimoto’s thyroiditis (HT) due to novel point mutation in the 11th exon of the THRB gene (c. 1378 G > A). The proband complained of goitre with increased thyroid hormone and normal thyroid stimulating hormone levels. Gene sequencing was performed to confirm the diagnosis. HT was also diagnosed based on positive thyroid autoantibodies and diffuse, grid-like changes in the thyroid on ultrasound examination. Additionally, a comprehensive examination of the proband’s pedigree was conducted. The patient’s father exhibited the same gene mutation site and was diagnosed with THRS and HT. No mutation site was detected in three patients with HT only and three healthy volunteers. Thus, gene sequencing should be considered the gold standard for diagnosing THRS. Furthermore, treatment should be individualized to control the patient’s symptoms rather than normalizing thyroid hormone levels. Further studies that determine the relationship between THRS and TH are warranted.

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Section: Discussionmentioning

confidence: 99%

Thyroid hormone resistance syndrome due to a novel heterozygous mutation and concomitant Hashimoto’s Thyroiditis: A pedigree report

Xie

et al. 2022

J Int Med Res

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“…All the mice were maintained under a 12-h light/dark cycle (lights on at 08:00 and off at 20:00) and had access to food and water ad libitum prior to the commencement of the study. The maintenance conditions were as follows: ambient temperature of 22 ± 1°C, humidity of 55 ± 5%, and light intensity of ≈ 100 lux ( Zhang et al, 2017 ; Liang et al, 2021 ). All animal handling procedures and experiments were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and all animal experimental procedures were approved by the Animal Care and Use Committee of Anhui Medical University ( Wang et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Effect of Restricted Feeding on Metabolic Health and Sleep-Wake Rhythms in Aging Mice

Qian

et al. 2021

Front. Neurosci.

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Aging, an irreversible and unavoidable physiological process in all organisms, is often accompanied by obesity, diabetes, cardiovascular diseases, sleep disorders, and fatigue. Thus, older adults are more likely to experience metabolic symptoms and sleep disturbances than are younger adults. Restricted feeding (RF) is a dietary regimen aimed at improving metabolic health and extending longevity, as well as reorganizing sleep-wake cycles. However, the potential of RF to improve metabolic health and sleep quality in older adults who are known to show a tendency toward increased weight gain and decreased sleep is unknown. To elucidate this issue, aged mice were assigned to an RF protocol during the active phase for 2 h per day for 2 weeks. Sleep-wake cycles were recorded during the RF regime in RF group and control mice. At the end of this period, body weight and blood biochemistry profiles, including blood glucose, cholesterol, and enzyme activity, in addition to dopamine concentrations in the brain, were measured in the RF group and age-matched controls. RF for 2 weeks improved the metabolic health of aged mice by reducing their body weights and blood glucose and cholesterol levels. At the beginning of the RF regime, sleep decreased in the dark period but not in the light period. After stable food entrainment was achieved (7 days post-RF commencement), the amount of time spent in wakefulness during the light period dramatically increased for 2 h before food availability, thereby increasing the mean duration of awake episodes and decreasing the number of wakefulness episodes. There was no significant difference in the sleep-wake time during the dark period in the RF group, with similar total amounts of wakefulness and sleep in a 24-h period to those of the controls. During the RF regime, dopamine levels in the midbrain increased in the RF group, pointing to its potential as the mechanism mediating metabolic symptoms and sleep-wake regulation during RF. In conclusion, our study suggested that RF during aging might prohibit or delay the onset of age-related diseases by improving metabolic health, without having a severe deleterious effect on sleep.

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“…Then, mouse studies reported that mutations in TRα resulted in intestinal defects, such as shorter villi, reduced apoptosis of the villi, reduced cell proliferation of the crypts, and decreased sucrase, lactase, and aminopeptidase enzymatic activities of the intestine ( 1 , 19 , 20 ). Recently, our group established a new TRα mutant mouse model ( Thra E403X/E403X mouse), and we observed that the length of the small and large intestine was significantly shorter, the number of epithelial cells was reduced, and the length of the villi and the depth of the crypts were significantly decreased in 3-week-old Thra E403X/E403X mice compared to Thra +/+ mice ( 21 ). These findings indicated that TRα1 plays an important role in intestinal development, which could be associated with the short lifespan and impaired postnatal development of Thra E403X/E403X mice.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of the Intestinal Resistance to Thyroid Hormone Mouse Model With Thyroid Hormone Receptor Alpha Mutations

Zhang²,

Liang

et al. 2022

Front. Endocrinol.

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Thyroid hormone is critical during the development of vertebrates and affects the function of many organs and tissues, especially the intestine. Triiodothyronine (T3) is the active form and can bind to thyroid hormone nuclear receptors (TRs) to play a vital role in the development of vertebrates. The resistance to thyroid hormone α, as seen in patients, has been mimicked by the ThraE403X mutation. To investigate the mechanisms underlying the effect of TRα1 on intestinal development, the present study employed proteomic analysis to identify differentially expressed proteins (DEPs) in the distal ileum between homozygous ThraE403X/E403X and wild-type Thra+/+ mice. A total of 1,189 DEPs were identified, including 603 upregulated and 586 downregulated proteins. Proteomic analysis revealed that the DEPs were highly enriched in the metabolic process, the developmental process, the transporter of the nutrients, and the intestinal immune system-related pathway. Of these DEPs, 20 proteins were validated by parallel reaction monitoring analysis. Our intestinal proteomic results provide promising candidates for future studies, as they suggest novel mechanisms by which TRα1 may influence intestinal development, such as the transport of intestinal nutrients and the establishment of innate and adaptive immune barriers of the intestine.

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Generation and Characterization of a New Resistance to Thyroid Hormone Mouse Model with Thyroid Hormone Receptor Alpha Gene Mutation

Cited by 5 publications

References 42 publications

Thyroid hormone resistance syndrome due to a novel heterozygous mutation and concomitant Hashimoto’s Thyroiditis: A pedigree report

Thyroid hormone resistance syndrome due to a novel heterozygous mutation and concomitant Hashimoto’s Thyroiditis: A pedigree report

Effect of Restricted Feeding on Metabolic Health and Sleep-Wake Rhythms in Aging Mice

Proteomic Analysis of the Intestinal Resistance to Thyroid Hormone Mouse Model With Thyroid Hormone Receptor Alpha Mutations

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