Parent-of-origin allelic contributions to deiodinase-3 expression elicit localized hyperthyroid milieu in the hippocampus

Sittig, Laura J.; Herzing, Laura B. K.; Shukla, Pradeep Kumar; Redei, Eva E.

doi:10.1038/mp.2011.19

Cited by 23 publications

(51 citation statements)

References 9 publications

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“…14 It is thus possible that different epigenetic factors control its transcription. Furthermore, preferential expression from the maternal Dio3 allele has been described in the adult rat hippocampus, 15 a tissue in which the larger Dio3 transcript accounts for the vast majority of Dio3 expression. 16 It is thus plausible that the larger DIO3 transcript, more abundant in adult tissues, 17 exhibits an allelic pattern of expression that is opposite to that observed for the shorter, development-associated Dio3 transcript.…”

Section: Discussionmentioning

confidence: 99%

Genomic imprinting of DIO3, a candidate gene for the syndrome associated with human uniparental disomy of chromosome 14

et al. 2016

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Individuals with uniparental disomy of chromosome 14 (Temple and Kagami-Ogata syndromes) exhibit a number of developmental abnormalities originating, in part, from aberrant developmental expression of imprinted genes in the DLK1-DIO3 cluster. Although genomic imprinting has been reported in humans for some genes in the cluster, little evidence is available about the imprinting status of DIO3, which modulates developmental exposure to thyroid hormones. We used pyrosequencing to evaluate allelic expression of DLK1 and DIO3 in cDNAs prepared from neonatal foreskins carrying single-nucleotide polymorphisms (SNPs) in the exonic sequence of those genes, and hot-stop PCR to quantify DIO3 allelic expression in cDNA obtained from a skin specimen collected from an adult individual with known parental origin of the DIO3 SNP. In neonatal skin, DLK1 and DIO3 both exhibited a high degree of monoallelic expression from the paternal allele. In the adult skin sample, the allele preferentially expressed is that inherited from the mother, although a different, larger DIO3 mRNA transcript appears the most abundant at this stage. We conclude that DIO3 is an imprinted gene in humans, suggesting that alterations in thyroid hormone exposure during development may partly contribute to the phenotypes associated with uniparental disomy of chromosome 14.

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Section: Discussionmentioning

confidence: 99%

Genomic imprinting of DIO3, a candidate gene for the syndrome associated with human uniparental disomy of chromosome 14

et al. 2016

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“…Expression levels of several imprinted genes are variable between sexes in the developing brain, even before the presence of any sex hormones in the body (Faisal et al, 2014). Differential genomic imprinting in the brain according to the sex of an individual (Gregg et al, 2010) would be the reason for this expression differences, since changes in imprinting status can alter transcript levels of imprinted genes (Sittig et al, 2011a). Sex differences in the expression of Igf2 and Insr are likely regulated by sex chromosome-related mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Modeling Fetal Alcohol Spectrum Disorder: Validating an Ex Vivo Primary Hippocampal Cell Culture System

Tunc-Ozcan

Ferreira

Redei

2016

Alcoholism Clin & Exp Res

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Background Fetal Alcohol Spectrum Disorder (FASD) is the leading non-genetic cause of mental retardation. There are no treatments for FASD to date. Preclinical in vivo and in vitro studies could help in identifying novel drug targets as for other diseases. Here, we describe an ex vivo model that combines the physiological advantages of prenatal ethanol (E) exposure in vivo with the uniformity of primary fetal hippocampal culture to characterize the effects of prenatal E. The insulin signaling pathways are known to be involved in hippocampal functions. Therefore, we compared the expression of insulin signaling pathway genes between fetal hippocampi (in vivo) and primary hippocampal culture (ex vivo). The similarity of prenatal E effects in these two paradigms would deem the ex vivo culture acceptable to screen possible treatments for FASD. Methods Pregnant Sprague-Dawley rats received one of three diets: ad libitum standard lab chow (control-C), isocaloric pair-fed (PF, nutritional control), and E containing liquid diets from gestational day (GD) 8. Fetal male and female hippocampi were collected either on GD21 (in vivo) or on GD18 for primary culture (ex vivo). Transcript levels of Igf2, Igf2r, Insr, Grb10, Rasgrf1 and Zac1 were measured by RT-qPCR. Results Hippocampal transcript levels differed by prenatal treatment in both males and females with sex differences observed in the expression of Igf2 and Insr. The effect of prenatal E on the hippocampal expression of the insulin pathway genes was parallel in the in vivo and the ex vivo conditions. Conclusions The similarity of gene expression changes in response to prenatal E between the in vivo and the ex vivo conditions ascertain that these effects are already set in the fetal hippocampus at GD18. This strengthens the feasibility of the ex vivo primary hippocampal culture as a tool to test and screen candidate drug targets for FASD.

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“…Brains were directly placed into RNAlater© (Life technologies, Grand Island, NY). Whole hippocampus was dissected as previously described (Sittig et al, 2011). RNA was isolated by the Trizol© reagent (Life technologies, Grand Island, NY), then converted to cDNA by ABI Reverse Transcription kit (Foster City, CA).…”

Section: Methodsmentioning

confidence: 99%

“…the globus pallidus and hypothalamus (Gregg et al, 2010; Pham et al, 1998). Since changes in imprinting status can alter transcript levels of imprinted genes (Sittig et al, 2011), conditions that change the imprinting status of Igf2 could have lasting effects on learning and memory by affecting the transcript levels. Gestational nutrition might be one such condition, since rodents born of diabetic mothers show altered non-neuronal Igf2 levels with concomitant increased methylation (Ding et al, 2012), while decreased methylation alters non-neuronal IGF2 transcript levels in humans born during famine (Heijmans et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Intergenerational and parent of origin effects of maternal calorie restriction on Igf2 expression in the adult rat hippocampus

Harper

Tunc-Ozcan

Graf

et al. 2014

Psychoneuroendocrinology

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Insulin-like growth factor 2 (Igf2) regulates development, memory and adult neurogenesis in the hippocampus. Calorie restriction (CR) is known to modulate non-neuronal Igf2 expression intergenerationally, but its effect has not been evaluated on brain Igf2. Here, Sprague-Dawley (S) dams underwent moderate CR between gestational days 8–21. To identify parent of origin expression pattern of the imprinted Igf2 gene, their offspring (SS F1) were mated with naïve male or female Brown Norway (B) rats to obtain the second generation (BS and SB F2) progeny. CR did not affect adult hippocampal Igf2 transcript levels in SS F1 males or their BS F2 progeny, but increased it in SS F1 females and their SB F2 offspring. The preferentially maternal Igf2 expression in the SB F2 control male hippocampus relaxed to biallelic with CR, with no effect of grandmaternal diet in any other groups. Thus, allele-specific and total expression of hippocampal Igf2 is affected by maternal, grandmaternal CR in a strain and sex-specific manner.

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Parent-of-origin allelic contributions to deiodinase-3 expression elicit localized hyperthyroid milieu in the hippocampus

Cited by 23 publications

References 9 publications

Genomic imprinting of DIO3, a candidate gene for the syndrome associated with human uniparental disomy of chromosome 14

Genomic imprinting of DIO3, a candidate gene for the syndrome associated with human uniparental disomy of chromosome 14

Modeling Fetal Alcohol Spectrum Disorder: Validating an Ex Vivo Primary Hippocampal Cell Culture System

Intergenerational and parent of origin effects of maternal calorie restriction on Igf2 expression in the adult rat hippocampus

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