Secisbp2 Is Essential for Embryonic Development and Enhances Selenoprotein Expression

Seeher, Sandra; Atassi, Tarik; Mahdi, Yassin; Carlson, Bradley A.; Braun, Doreen; Wirth, Eva K.; Klein, Marc; Reix, Nathalie; Miniard, Angela C.; Schomburg, Lutz; Hatfield, Dolph L.; Driscoll, Donna M.; Schweizer, Ulrich

doi:10.1089/ars.2013.5358

Cited by 67 publications

(65 citation statements)

References 63 publications

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“…Secisbp2 is essential for embryonic development [24]. In order to investigate its function in neurons, we specifically inactivated the Secisbp2 gene by an out-of-frame deletion of exon 5 using a CamK-Cre transgene (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Transgenic Secisbp2 tm1a(EUCOMM)Wtsi mice were described recently [24]. The breeding colony was maintained on breeding diets (Ssniff, Soest, Germany) containing on average 0.2-0.3 ppm Se.…”

Section: Methodsmentioning

confidence: 99%

“…The insulin-dependent fluorescent Txnrd assay from IMCO (Stockholm, Sweden) was used to determine selenium-dependent Txnrd activities as described [24]. The Txnrd standards were adjusted to be within the range of our samples [in nM]: 0.125, 0.25, 0.375, 0.50, 0.625, 0.75, 0.825, 1.0.…”

Section: Methodsmentioning

confidence: 99%

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Impaired selenoprotein expression in brain triggers striatal neuronal loss leading to co-ordination defects in mice

Seeher

Carlson

Miniard

et al. 2014

Biochemical Journal

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Selenocysteine Insertion Sequence (SECIS)-Binding Protein 2 (Secisbp2) binds to SECIS elements located in the 3′-untranslated region of eukaryotic selenoprotein mRNAs. It facilitates incorporation of the rare amino acid selenocysteine in response to UGA codons. Inactivation of Secisbp2 in hepatocytes greatly reduced selenoprotein levels. Neuron-specific inactivation of Secisbp2 (CamK-Cre; Secisbp2fl/fl) reduced cerebral expression of selenoproteins to a lesser extent than inactivation of tRNA[Ser]Sec. This allowed us to study the development of cortical parvalbumin-positive (PV+) interneurons, which are completely lost in tRNA[Ser]Sec mutants. PV+ interneuron density was reduced in the somatosensory cortex, hippocampus, and striatum. In situ-hybridization for Gad67 confirmed the reduction of GABAergic interneurons. Because of the obvious movement phenotype involving a broad, dystonic gait, we suspected basal ganglia dysfunction. Tyrosine hydroxylase expression was normal in substantia nigra neurons and their striatal terminals. However the densities of striatal PV+ and Gad67+ neurons were decreased by 65% and 49%, respectively. Likewise, the density of striatal cholinergic neurons was reduced by 68%. Our observations demonstrate that several classes of striatal interneurons depend on selenoprotein expression. These findings may offer an explanation for the movement phenotype of selenoprotein P-deficient mice and the movement disorder and mental retardation described in a patient carrying SECISBP2 mutations.

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Section: Resultsmentioning

confidence: 99%

“…Transgenic Secisbp2 tm1a(EUCOMM)Wtsi mice were described recently [24]. The breeding colony was maintained on breeding diets (Ssniff, Soest, Germany) containing on average 0.2-0.3 ppm Se.…”

Section: Methodsmentioning

confidence: 99%

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Impaired selenoprotein expression in brain triggers striatal neuronal loss leading to co-ordination defects in mice

Seeher

Carlson

Miniard

et al. 2014

Biochemical Journal

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“…To further analyze SBP2 function in organs not accessible in patients, mice models have been developed. While gene inactivation leads to embryonic lethality (123), the conditional deletion of SBP2 is less detrimental than Sec-tRNA [Ser]Sec inactivation and provides a tool for further in vivo functional analysis (124).…”

Section: The Secis Binding Protein 2 (Sbp2)mentioning

confidence: 99%

Update on Selenoprotein Biosynthesis

Bulteau

Chavatte

2015

Antioxidants & Redox Signaling

122

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The regulation of selenoproteins in response to a variety of pathophysiological conditions and cellular stressors, including selenium levels, oxidative stress, replicative senescence, or cancer, awaits further detailed investigation. Clearly, the efficiency of UGA-selenocysteine recoding is the limiting stage of selenoprotein synthesis. The sequence of events leading Sec-tRNA([Ser]Sec) delivery to ribosomal A site awaits further analysis, notably at the level of a three-dimensional structure.

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“…We have previously reported that hepatocyte-specific inactivation of selenoprotein translation abrogated hepatic deiodinase activity in Alb-Cre ; Trsp fl/fl mice [13]. Expression of all selenoproteins is quantitatively abolished in livers of Alb-Cre ; Trsp fl/fl mice [15]. Ablation of selenoprotein biosynthesis in hepatocytes does not lead to liver failure or other diseases [16,17].…”

Section: Resultsmentioning

confidence: 99%

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase

et al. 2015

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Background: The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T₃, low T₄). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). Objective: To test the hypothesis that circulating low T₄ and high T₃ levels are caused by enhanced conversion of T₄ via increased activity of hepatic type I deiodinase (Dio1). Methods: We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results: Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Conclusions: Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated.

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Secisbp2 Is Essential for Embryonic Development and Enhances Selenoprotein Expression

Abstract: In hepatocyte-specific conditional mouse models, Secisbp2 gene inactivation is less detrimental than tRNA[Ser]Sec inactivation. A role of Secisbp2 in stabilizing selenoprotein mRNAs in vivo was uncovered.

Cited by 67 publications

References 63 publications

Impaired selenoprotein expression in brain triggers striatal neuronal loss leading to co-ordination defects in mice

Impaired selenoprotein expression in brain triggers striatal neuronal loss leading to co-ordination defects in mice

Update on Selenoprotein Biosynthesis

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase

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