Expression of the diabetes‐associated gene <i>TCF7L2</i> in adult mouse brain

Lee, Syann; Lee, Charlotte E.; Elias, Carol F.; Elmquist, Joel K.

doi:10.1002/cne.22199

Cited by 23 publications

(28 citation statements)

References 66 publications

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“…Lee and collaborators reported high TCF7L2 expression in thalamic and tectal adult mouse brain structures, with lower expression level in the hypothalamus and additional areas [66]. Further studies showed that TCF7L2 expression in the CNS is characterized by a variety of splice variants.…”

Section: Discussionmentioning

confidence: 98%

Association of the Type 2 Diabetes Mellitus Susceptibility Gene, TCF7L2, with Schizophrenia in an Arab-Israeli Family Sample

et al. 2012

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Many reports in different populations have demonstrated linkage of the 10q24–q26 region to schizophrenia, thus encouraging further analysis of this locus for detection of specific schizophrenia genes. Our group previously reported linkage of the 10q24–q26 region to schizophrenia in a unique, homogeneous sample of Arab-Israeli families with multiple schizophrenia-affected individuals, under a dominant model of inheritance. To further explore this candidate region and identify specific susceptibility variants within it, we performed re-analysis of the 10q24-26 genotype data, taken from our previous genome-wide association study (GWAS) (Alkelai et al, 2011). We analyzed 2089 SNPs in an extended sample of 57 Arab Israeli families (189 genotyped individuals), under the dominant model of inheritance, which best fits this locus according to previously performed MOD score analysis. We found significant association with schizophrenia of the TCF7L2 gene intronic SNP, rs12573128, (p = 7.01×10−6) and of the nearby intergenic SNP, rs1033772, (p = 6.59×10−6) which is positioned between TCF7L2 and HABP2. TCF7L2 is one of the best confirmed susceptibility genes for type 2 diabetes (T2D) among different ethnic groups, has a role in pancreatic beta cell function and may contribute to the comorbidity of schizophrenia and T2D. These preliminary results independently support previous findings regarding a possible role of TCF7L2 in susceptibility to schizophrenia, and strengthen the importance of integrating linkage analysis models of inheritance while performing association analyses in regions of interest. Further validation studies in additional populations are required.

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Section: Discussionmentioning

confidence: 98%

Association of the Type 2 Diabetes Mellitus Susceptibility Gene, TCF7L2, with Schizophrenia in an Arab-Israeli Family Sample

et al. 2012

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“…These studies, however, have re-directed our attention to the expression and function of Tcf7l2 and Wnt signaling in pancreatic islets, especially in the pancreatic b cells. Tcf7l2 is abundantly expressed in the mouse intestinal epithelia and adipocytes (Barker et al 1999, Ross et al 2000, and in the central nervous system (Lee et al 2009). Inconsistent findings about Tcf7l2 expression in the mouse pancreas, however, can be found in the literature.…”

Section: Discussionmentioning

confidence: 99%

Insulin treatment and high-fat diet feeding reduces the expression of three Tcf genes in rodent pancreas

Columbus¹,

Chiang²,

Shao³

et al. 2010

Journal of Endocrinology

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Specific single-nucleotide polymorphisms in intronic regions of human TCF7L2 are associated with an elevated risk of developing type 2 diabetes. Whether Tcf7l2 is expressed in pancreatic islets of rodent species at a considerable level, however, remains controversial. We used RT-PCR and quantitative RT-PCR to examine Tcf7l2 expression in rodent gut, pancreas, isolated pancreatic islets, and cultured cell lines. The expression level of Tcf7l2 was relatively lower in the pancreas compared to the gut or the pancreatic b-cell line Ins-1. Immunostaining did not detect a Tcf7l2 signal in mouse pancreatic islets. Endogenous canonical Wnt activity was not appreciable in the pancreas of TOPGAL transgenic mice. Both Tcf7 and Tcf7l1, but not Lef1, were expressed in the pancreas. The expression of the three Tcf genes (Tcf7, Tcf7l1, and Tcf7l2) in the pancreas was reduced by treatment with insulin or high-fat diet feeding, in contrast to the stimulation of Tcf7l2 expression by insulin in the gut. We suggest that hyperinsulinemia represses Tcf gene expression in the pancreas. Whether and how this reduction alters the function of pancreatic b cells during hyperinsulinemia deserves further investigation.

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“…The antisera used in the present study are all commercially available, have been validated before and used by different laboratories (Scott et al, 2009); (Zhao et al, 2008); (Lee et al, 2009); (Clarkson et al, 2009, Caron et al, 2010). …”

Section: Methodsmentioning

confidence: 99%

Characterization of Kiss1 neurons using transgenic mouse models

et al. 2011

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Humans and mice with loss-of-function mutations of the genes encoding kisspeptins (Kiss1) or kisspeptin receptors (Kiss1r) are infertile due to hypogonadotropic hypogonadism. Within the hypothalamus, Kiss1 mRNA is expressed in the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (Arc). In order to better study the different populations of kisspeptin cells we generated Kiss1-Cre transgenic mice. We obtained one line with Cre activity specifically within Kiss1 neurons (line J2-4), as assessed by generating mice with Cre-dependent expression of green fluorescent protein or β-galactosidase. Also, we demonstrated Kiss1 expression in the cerebral cortex and confirmed previous data showing Kiss1 mRNA in the medial nucleus of amygdala and anterodorsal preoptic nucleus. Kiss1 neurons were more concentrated towards the caudal levels of the Arc and higher leptin-responsivity was observed in the most caudal population of Arc Kiss1 neurons. No evidence for direct action of leptin in AVPV Kiss1 neurons was observed. Melanocortin fibers innervated subsets of Kiss1 neurons of the preoptic area and Arc, and both populations expressed MC4R. Specifically in the preoptic area, 18-28% of Kiss1 neurons expressed MC4R. In the Arc, 90% of Kiss1 neurons were glutamatergic, 50% of which also were GABAergic. In the AVPV, 20% of Kiss1 neurons were glutamatergic whereas 75% were GABAergic. The differences observed between the Kiss1 neurons in the preoptic area and the Arc likely represent neuronal evidence for their differential roles in metabolism and reproduction.

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Expression of the diabetes‐associated gene TCF7L2 in adult mouse brain

Cited by 23 publications

References 66 publications

Association of the Type 2 Diabetes Mellitus Susceptibility Gene, TCF7L2, with Schizophrenia in an Arab-Israeli Family Sample

Association of the Type 2 Diabetes Mellitus Susceptibility Gene, TCF7L2, with Schizophrenia in an Arab-Israeli Family Sample

Insulin treatment and high-fat diet feeding reduces the expression of three Tcf genes in rodent pancreas

Characterization of Kiss1 neurons using transgenic mouse models

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