Delayed development of specific thyroid hormone-regulated events in transthyretin null mice

Monk, Julie A.; Sims, Natalie A.; Dzięgielewska, Katarzyna M.; Weiss, Roy E.; Ramsay, Robert G.; Richardson, Samantha J.

doi:10.1152/ajpendo.00216.2012

Cited by 32 publications

(21 citation statements)

References 64 publications

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“…In this study, shRNA that silenced TTR , was used to investigate (i) inhibition of myotube formation based on MYOG and MYL2 mRNA expression (ii) changes in mRNA expression of the calcium channel related genes, STIM1, Orai1, Cav1.1 and Cav3.1, and (iii) time dependent occurrence of voltage-gated calcium currents during myogenesis. Our results are in accordance with Mock et al [35], in which they demonstrate the decrease in muscle mass of a TTR null mouse.…”

Section: Discussionsupporting

confidence: 94%

Transthyretin Is a Key Regulator of Myoblast Differentiation

et al. 2013

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Transthyretin (TTR) is a known carrier protein for thyroxine (T4) and retinol-binding protein in the blood that is primarily synthesized in the liver and choroid plexus of the brain. Herein, we report that the TTR gene is expressed in skeletal muscle tissue and up-regulated during myotube formation in C2C12 cells. TTR silencing (TTRkd) significantly reduced myogenin expression and myotube formation, whereas myogenin silencing (MYOGkd) did not have any effect on TTR gene expression. Both TTRkd and MYOGkd led to a decrease in calcium channel related genes including Cav1.1, STIM1 and Orai1. A significant decrease in intracellular T4 uptake during myogenesis was observed in TTRkd cells. Taken together, the results of this study suggest that TTR initiates myoblast differentiation via affecting expression of the genes involved during early stage of myogenesis and the genes related to calcium channel.

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Section: Discussionsupporting

confidence: 94%

Transthyretin Is a Key Regulator of Myoblast Differentiation

et al. 2013

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“…Another likely candidate is transthyretin, whose synthesis in the brain is restricted to choroid plexus. The transthyretin gene is highly expressed throughout development in rat choroid plexus ([52] and data not shown), and this thyroxin carrier was shown to be important and necessary for various aspects of normal brain development [53]. …”

Section: Resultsmentioning

confidence: 99%

Developmental changes in the transcriptome of the rat choroid plexus in relation to neuroprotection

Kratzer

Liddelow

Saunders

et al. 2013

Fluids Barriers CNS

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BackgroundThe choroid plexuses are the interface between the blood and the cerebrospinal fluid (CSF) contained within the ventricular spaces of the central nervous system. The tight junctions linking adjacent cells of the choroidal epithelium create a physical barrier to paracellular movement of molecules. Multispecific efflux transporters as well as drug-metabolizing and antioxidant enzymes functioning in these cells contribute to a metabolic barrier. These barrier properties reflect a neuroprotective function of the choroid plexus. The choroid plexuses develop early during embryogenesis and provide pivotal control of the internal environment throughout development when the brain is especially vulnerable to toxic insults. Perinatal injuries like hypoxia and trauma, and exposure to drugs or toxic xenobiotics can have serious consequences on neurogenesis and long-term development. The present study describes the developmental expression pattern of genes involved in the neuroprotective functions of the blood–CSF barrier.MethodsThe transcriptome of rat lateral ventricular choroid plexuses isolated from fifteen-day-old embryos, nineteen-day old fetuses, two-day old pups, and adults was analyzed by a combination of Affymetrix microarrays, Illumina RNA-Sequencing, and quantitative RT-PCR.ResultsGenes coding for proteins involved in junction formation are expressed early during development. Overall perinatal expression levels of genes involved in drug metabolism and antioxidant mechanisms are similar to, or higher than levels measured in adults. A similar developmental pattern was observed for multispecific efflux transporter genes of the Abc and Slc superfamilies. Expression of all these genes was more variable in choroid plexus from fifteen-day-old embryos. A large panel of transcription factors involved in the xenobiotic- or cell stress-mediated induction of detoxifying enzymes and transporters is also expressed throughout development.ConclusionsThis transcriptomic analysis suggests relatively well–established neuroprotective mechanisms at the blood-CSF barrier throughout development of the rat. The expression of many transcription factors early in development raises the possibility of additional protection for the vulnerable developing brain, should the fetus or newborn be exposed to drugs or other xenobiotics.

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“…11–13 Mice with both copies of the gene silenced display a behavioral abnormality throughout life, and it has been suggested that they exhibit a physical developmental delay that normalizes in young adults. 14–16 …”

Section: The Ttr Gene and Proteinmentioning

confidence: 99%

Transthyretin V122I (pV142I)* cardiac amyloidosis: an age-dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans

Buxbaum

Ruberg

2017

Genetics in Medicine

131

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Since the identification of a valine-to-isoleucine substitution at position 122 (TTR V122I; pV142I) in the transthyretin (TTR)-derived fibrils extracted from the heart of a patient with late-onset cardiac amyloidosis, it has become clear that the amyloidogenic mutation and the disease occur almost exclusively in individuals of identifiable African descent. In the United States, the amyloidogenic allele frequency is 0.0173 and is carried by 3.5% of community-dwelling African Americans. Genotyping across Africa indicates that the origin of the allele is in the West African countries that were the major source of the slave trade to North America. At autopsy, the allele was found to be associated with cardiac TTR amyloid deposition in all the carriers after age 65 years; however, the clinical penetrance varies, resulting in substantial heart disease in some carriers and few symptoms in others. The allele has been found in 10% of African Americans older than age 65 with severe congestive heart failure. At this time there are potential forms of therapy in clinical trials. The combination of a highly accurate genetic test and the potential for specific therapy demands a greater awareness of this autosomal dominant, age-dependent cardiac disease in the cardiology community.

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Delayed development of specific thyroid hormone-regulated events in transthyretin null mice

Cited by 32 publications

References 64 publications

Transthyretin Is a Key Regulator of Myoblast Differentiation

Transthyretin Is a Key Regulator of Myoblast Differentiation

Developmental changes in the transcriptome of the rat choroid plexus in relation to neuroprotection

Transthyretin V122I (pV142I)* cardiac amyloidosis: an age-dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans

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