A novel mutation in the thyroglobulin gene that causes goiter and dwarfism in Wistar Hannover GALAS rats

Sato, Akira; Abe, Kuniya; Yuzuriha, Misako; Fujii, Sakiko; Takahashi, Naofumi; Hojo, Hitoshi; Teramoto, Shoji; Aoyama, Hiroaki

doi:10.1016/j.mrfmmm.2014.02.003

Cited by 12 publications

(5 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Defects in pre-mRNA splicing have been shown as a common disease-causing mechanism in a considerable number of pathophysiological entities, either by altering positions of ss sequences or by affecting intronic or exonic splicing regulatory sequences such as ESE elements (Bonnet et al, 2008;Tournier et al, 2008). In particular, a missplicing of TG pre-mRNA due to a mutation in consensus splice donor or acceptor site is known to induce a congenital goiter and hypothyroidism in humans (Abdul-Hassan et al, 2013;Alzahrani et al, 2006;Gutnisky et al, 2004;Hermanns et al, 2013;Hishinuma et al, 2006;Ieiri et al, 1991;Narumi et al, 2011;Niu et al, 2009;Pardo et al, 2008Pardo et al, , 2009Peteiro-Gonzalez et al, 2010;Targovnik et al, 1995Targovnik et al, , 2001Targovnik et al, , 2012 and rodents (Sato et al, 2014). The usefulness of splicing reporter minigene assays has been shown to be a good approach to determine the effect of the variants on the splicing process, (Bonnet et al, 2008;Tournier et al, 2008), when genes present a restricted expression profile or is difficult to obtain RNA from patients' tissues.…”

Section: Discussionmentioning

confidence: 99%

Novel compound heterozygous Thyroglobulin mutations c.745+1G>A/c.7036+2T>A associated with congenital goiter and hypothyroidism in a Vietnamese family. Identification of a new cryptic 5′ splice site in the exon 6

Citterio

Morales

Bouhours‐Nouet

et al. 2015

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Novel compound heterozygous Thyroglobulin mutations c.745+1G>A/c.7036+2T>A associated with congenital goiter and hypothyroidism in a Vietnamese family. Identification of a new cryptic 5′ splice site in the exon 6

Citterio

Morales

Bouhours‐Nouet

et al. 2015

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

“…The reported human monomer TG molecular mass is 330 kDa, containing nearly 2750 AA residues, comprising type I, II, and III repeat motif-containing regions and the C-terminal cholinesterase-like domain [17]. Patients and rodent models with tg gene mutations typically develop hypothyroidism goiters [18,19]. However, it is possible that certain weak genetic variations within the tg locus contribute to euthyroid familial goiters.…”

Section: Introductionmentioning

confidence: 99%

Functions of the Thyroid-Stimulating Hormone on Key Developmental Features Revealed in a Series of Zebrafish Dyshormonogenesis Models

Song

Cheng

et al. 2021

Cells

View full text Add to dashboard Cite

The hypothalamic–pituitary–thyroid (HPT) axis regulates many critical features in vertebrates. Utilizing TALENs and CRISPR/Cas9 techniques, thyroid-stimulating hormone subunit beta a (tshba), thyroglobulin (tg), and solute carrier family 16 member 2 (slc16a2) mutant zebrafish lines were generated. Among the three mutants, the earliest time point for the significantly altered T3 contents was observed in tshba mutants, which resulted in the most severe defects, including typical defects such as the retardation of inflated anterior swimming bladder (aSB), proper formation of fin ray and posterior squamation (SP), the larval-to-juvenile transition (LTJT) process, juvenile growth retardation, and mating failure. In tg mutants, which are actually compensated with an alternative splicing form, growth retardation was observed in the juvenile stage without LTJT and reproductive defects. The evident goiter phenotype was only observed in tg- and slc16a2 mutants, but not in tshba mutants. Other than goiters being observed, no other significant developmental defects were found in the slc16a2 mutants. Regarding the reproductive defects observed in tshba mutants, the defective formation of the secondary sex characteristics (SSCs) was observed, while no obvious alterations during gonad development were found. Based on our analyses, zebrafish at the 6–12 mm standard length or 16–35 days post-fertilization (dpf) should be considered to be in their LTJT phase. Using a series of zebrafish dyshormonogenesis models, this study demonstrated that the TSH function is critical for the proper promotion of zebrafish LTJT and SSC formation. In addition, the elevation of TSH levels appears to be essential for goiter appearance in zebrafish.

show abstract

“…Nevertheless, we cannot exclude the possibility that aht was caused by a mutation in the non‐coding region of Dsp . For example, goiter and dwarfism in rats can be caused by a single‐nucleotide substitution at the acceptor site of the intron of the thyroglobulin gene 6 . Alternatively, aht may be caused by a mutation in a regulatory region of Dsp , altering the expression of this gene.…”

Section: Discussionmentioning

confidence: 99%

Recessive mutation on mouse chromosome 13 associated with abnormal hair texture and cardiomyopathy

Suto

2023

Congenital Anomalies

View full text Add to dashboard Cite

An autosomal recessive mutation (aht) associated with abnormal hair texture and cardiomyopathy spontaneously arose in the Y‐chromosome consomic mouse strain DH‐Chr YSS. The aht/aht mouse phenotypes closely resembled those of rul/rul mice, which were caused by a mutation in desmoplakin (Dsp) on chromosome 13. Quantitative trait locus (QTL) mapping using (DDD/Sgn × DH‐Chr YSS‐aht heterozygotes) F2 mice demonstrated that aht is contiguous with Dsp on chromosome 13. However, no nucleotide changes were identified in the coding region of Dsp in aht/aht mice by whole‐exome sequencing. Therefore, the molecular nature of the aht mutation remains unclear. Nevertheless, aht/aht mice may serve as a new model for human diseases that are accompanied by abnormalities in the integumental and cardiovascular systems, including Carvajal‐Huerta syndrome.

show abstract

A novel mutation in the thyroglobulin gene that causes goiter and dwarfism in Wistar Hannover GALAS rats

Cited by 12 publications

References 43 publications

Novel compound heterozygous Thyroglobulin mutations c.745+1G>A/c.7036+2T>A associated with congenital goiter and hypothyroidism in a Vietnamese family. Identification of a new cryptic 5′ splice site in the exon 6

Novel compound heterozygous Thyroglobulin mutations c.745+1G>A/c.7036+2T>A associated with congenital goiter and hypothyroidism in a Vietnamese family. Identification of a new cryptic 5′ splice site in the exon 6

Functions of the Thyroid-Stimulating Hormone on Key Developmental Features Revealed in a Series of Zebrafish Dyshormonogenesis Models

Recessive mutation on mouse chromosome 13 associated with abnormal hair texture and cardiomyopathy

Contact Info

Product

Resources

About