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description Publicationkeyboard_double_arrow_right Article , Other literature type , Journal 2017Embargo end date: 24 Jan 2018 Australia, Australia, United KingdomPublisher:Elsevier BV Funded by:WT, UKRI | Neurobehavioural genetics..., WT | Molecular and neural basi... +1 projectsWT ,UKRI| Neurobehavioural genetics. Isolation and characterisation of behavioural mutations in mice ,WT| Molecular and neural basis of obesity ,UKRI| Genetics of Type 2 DiabetesAdrienne E. Sullivan; I. Sadaf Farooqi; Susan Kirsch; Roger D. Cox; Cheryl L. Scudamore; Stephen O'Rahilly; Elizabeth Bentley; Patrick M. Nolan; Rasneer Sonia Bains; Inês Barroso; Elana Henning; Julia M. Keogh; Gareth Banks; Rebecca Dumbell; David C. Bersten; Murray L. Whitelaw; Murray L. Whitelaw; Michelle Simon; Lee Moir; Audrey E. Hendricks; Audrey E. Hendricks; Elena G. Bochukova; Elena G. Bochukova; Kimberly A. Watson;OBJECTIVE: Genetic studies in obese rodents and humans can provide novel insights into the mechanisms involved in energy homeostasis. METHODS: In this study, we genetically mapped the chromosomal region underlying the development of severe obesity in a mouse line identified as part of a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis screen. We characterized the metabolic and behavioral phenotype of obese mutant mice and examined changes in hypothalamic gene expression. In humans, we examined genetic data from people with severe early onset obesity. RESULTS: We identified an obese mouse heterozygous for a missense mutation (pR108W) in orthopedia homeobox (Otp), a homeodomain containing transcription factor required for the development of neuroendocrine cell lineages in the hypothalamus, a region of the brain important in the regulation of energy homeostasis. OtpR108W/+ mice exhibit increased food intake, weight gain, and anxiety when in novel environments or singly housed, phenotypes that may be partially explained by reduced hypothalamic expression of oxytocin and arginine vasopressin. R108W affects the highly conserved homeodomain, impairs DNA binding, and alters transcriptional activity in cells. We sequenced OTP in 2548 people with severe early-onset obesity and found a rare heterozygous loss of function variant in the homeodomain (Q153R) in a patient who also had features of attention deficit disorder. CONCLUSIONS: OTP is involved in mammalian energy homeostasis and behavior and appears to be necessary for the development of hypothalamic neural circuits. Further studies will be needed to investigate the contribution of rare variants in OTP to human energy homeostasis.
CORE arrow_drop_down Central Archive at the University of ReadingArticle . 2017License: CC BYData sources: CORE (RIOXX-UK Aggregator)CORE (RIOXX-UK Aggregator)Article . 2017License: http://llr.ntu.ac.uk/irep/reuseData sources: CORE (RIOXX-UK Aggregator)The University of Adelaide: Digital LibraryArticle . 2017License: CC BYFull-Text: http://hdl.handle.net/2440/129615Data sources: Bielefeld Academic Search Engine (BASE)Queen Mary University of London: Queen Mary Research Online (QMRO)Article . 2018License: CC BYData sources: Bielefeld Academic Search Engine (BASE)add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.molmet.2017.08.006&type=result"></script>'); --> </script>For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 16 citations 16 popularity Top 10% influence Average impulse Top 10% 
Powered by BIP!more_vert CORE arrow_drop_down Central Archive at the University of ReadingArticle . 2017License: CC BYData sources: CORE (RIOXX-UK Aggregator)CORE (RIOXX-UK Aggregator)Article . 2017License: http://llr.ntu.ac.uk/irep/reuseData sources: CORE (RIOXX-UK Aggregator)The University of Adelaide: Digital LibraryArticle . 2017License: CC BYFull-Text: http://hdl.handle.net/2440/129615Data sources: Bielefeld Academic Search Engine (BASE)Queen Mary University of London: Queen Mary Research Online (QMRO)Article . 2018License: CC BYData sources: Bielefeld Academic Search Engine (BASE)add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.molmet.2017.08.006&type=result"></script>'); --> </script>For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Other literature type , Journal 2017Embargo end date: 24 Jan 2018 Australia, Australia, United KingdomPublisher:Elsevier BV Funded by:WT, UKRI | Neurobehavioural genetics..., WT | Molecular and neural basi... +1 projectsWT ,UKRI| Neurobehavioural genetics. Isolation and characterisation of behavioural mutations in mice ,WT| Molecular and neural basis of obesity ,UKRI| Genetics of Type 2 DiabetesAdrienne E. Sullivan; I. Sadaf Farooqi; Susan Kirsch; Roger D. Cox; Cheryl L. Scudamore; Stephen O'Rahilly; Elizabeth Bentley; Patrick M. Nolan; Rasneer Sonia Bains; Inês Barroso; Elana Henning; Julia M. Keogh; Gareth Banks; Rebecca Dumbell; David C. Bersten; Murray L. Whitelaw; Murray L. Whitelaw; Michelle Simon; Lee Moir; Audrey E. Hendricks; Audrey E. Hendricks; Elena G. Bochukova; Elena G. Bochukova; Kimberly A. Watson;OBJECTIVE: Genetic studies in obese rodents and humans can provide novel insights into the mechanisms involved in energy homeostasis. METHODS: In this study, we genetically mapped the chromosomal region underlying the development of severe obesity in a mouse line identified as part of a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis screen. We characterized the metabolic and behavioral phenotype of obese mutant mice and examined changes in hypothalamic gene expression. In humans, we examined genetic data from people with severe early onset obesity. RESULTS: We identified an obese mouse heterozygous for a missense mutation (pR108W) in orthopedia homeobox (Otp), a homeodomain containing transcription factor required for the development of neuroendocrine cell lineages in the hypothalamus, a region of the brain important in the regulation of energy homeostasis. OtpR108W/+ mice exhibit increased food intake, weight gain, and anxiety when in novel environments or singly housed, phenotypes that may be partially explained by reduced hypothalamic expression of oxytocin and arginine vasopressin. R108W affects the highly conserved homeodomain, impairs DNA binding, and alters transcriptional activity in cells. We sequenced OTP in 2548 people with severe early-onset obesity and found a rare heterozygous loss of function variant in the homeodomain (Q153R) in a patient who also had features of attention deficit disorder. CONCLUSIONS: OTP is involved in mammalian energy homeostasis and behavior and appears to be necessary for the development of hypothalamic neural circuits. Further studies will be needed to investigate the contribution of rare variants in OTP to human energy homeostasis.
CORE arrow_drop_down Central Archive at the University of ReadingArticle . 2017License: CC BYData sources: CORE (RIOXX-UK Aggregator)CORE (RIOXX-UK Aggregator)Article . 2017License: http://llr.ntu.ac.uk/irep/reuseData sources: CORE (RIOXX-UK Aggregator)The University of Adelaide: Digital LibraryArticle . 2017License: CC BYFull-Text: http://hdl.handle.net/2440/129615Data sources: Bielefeld Academic Search Engine (BASE)Queen Mary University of London: Queen Mary Research Online (QMRO)Article . 2018License: CC BYData sources: Bielefeld Academic Search Engine (BASE)add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.molmet.2017.08.006&type=result"></script>'); --> </script>For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 16 citations 16 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert CORE arrow_drop_down Central Archive at the University of ReadingArticle . 2017License: CC BYData sources: CORE (RIOXX-UK Aggregator)CORE (RIOXX-UK Aggregator)Article . 2017License: http://llr.ntu.ac.uk/irep/reuseData sources: CORE (RIOXX-UK Aggregator)The University of Adelaide: Digital LibraryArticle . 2017License: CC BYFull-Text: http://hdl.handle.net/2440/129615Data sources: Bielefeld Academic Search Engine (BASE)Queen Mary University of London: Queen Mary Research Online (QMRO)Article . 2018License: CC BYData sources: Bielefeld Academic Search Engine (BASE)add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.molmet.2017.08.006&type=result"></script>'); --> </script>For further information contact us at helpdesk@openaire.eu
description Publicationkeyboard_double_arrow_right Article , Other literature type , Journal 2017Embargo end date: 24 Jan 2018 Australia, Australia, United KingdomPublisher:Elsevier BV Funded by:WT, UKRI | Neurobehavioural genetics..., WT | Molecular and neural basi... +1 projectsWT ,UKRI| Neurobehavioural genetics. Isolation and characterisation of behavioural mutations in mice ,WT| Molecular and neural basis of obesity ,UKRI| Genetics of Type 2 DiabetesAdrienne E. Sullivan; I. Sadaf Farooqi; Susan Kirsch; Roger D. Cox; Cheryl L. Scudamore; Stephen O'Rahilly; Elizabeth Bentley; Patrick M. Nolan; Rasneer Sonia Bains; Inês Barroso; Elana Henning; Julia M. Keogh; Gareth Banks; Rebecca Dumbell; David C. Bersten; Murray L. Whitelaw; Murray L. Whitelaw; Michelle Simon; Lee Moir; Audrey E. Hendricks; Audrey E. Hendricks; Elena G. Bochukova; Elena G. Bochukova; Kimberly A. Watson;OBJECTIVE: Genetic studies in obese rodents and humans can provide novel insights into the mechanisms involved in energy homeostasis. METHODS: In this study, we genetically mapped the chromosomal region underlying the development of severe obesity in a mouse line identified as part of a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis screen. We characterized the metabolic and behavioral phenotype of obese mutant mice and examined changes in hypothalamic gene expression. In humans, we examined genetic data from people with severe early onset obesity. RESULTS: We identified an obese mouse heterozygous for a missense mutation (pR108W) in orthopedia homeobox (Otp), a homeodomain containing transcription factor required for the development of neuroendocrine cell lineages in the hypothalamus, a region of the brain important in the regulation of energy homeostasis. OtpR108W/+ mice exhibit increased food intake, weight gain, and anxiety when in novel environments or singly housed, phenotypes that may be partially explained by reduced hypothalamic expression of oxytocin and arginine vasopressin. R108W affects the highly conserved homeodomain, impairs DNA binding, and alters transcriptional activity in cells. We sequenced OTP in 2548 people with severe early-onset obesity and found a rare heterozygous loss of function variant in the homeodomain (Q153R) in a patient who also had features of attention deficit disorder. CONCLUSIONS: OTP is involved in mammalian energy homeostasis and behavior and appears to be necessary for the development of hypothalamic neural circuits. Further studies will be needed to investigate the contribution of rare variants in OTP to human energy homeostasis.
CORE arrow_drop_down Central Archive at the University of ReadingArticle . 2017License: CC BYData sources: CORE (RIOXX-UK Aggregator)CORE (RIOXX-UK Aggregator)Article . 2017License: http://llr.ntu.ac.uk/irep/reuseData sources: CORE (RIOXX-UK Aggregator)The University of Adelaide: Digital LibraryArticle . 2017License: CC BYFull-Text: http://hdl.handle.net/2440/129615Data sources: Bielefeld Academic Search Engine (BASE)Queen Mary University of London: Queen Mary Research Online (QMRO)Article . 2018License: CC BYData sources: Bielefeld Academic Search Engine (BASE)add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.molmet.2017.08.006&type=result"></script>'); --> </script>For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 16 citations 16 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert CORE arrow_drop_down Central Archive at the University of ReadingArticle . 2017License: CC BYData sources: CORE (RIOXX-UK Aggregator)CORE (RIOXX-UK Aggregator)Article . 2017License: http://llr.ntu.ac.uk/irep/reuseData sources: CORE (RIOXX-UK Aggregator)The University of Adelaide: Digital LibraryArticle . 2017License: CC BYFull-Text: http://hdl.handle.net/2440/129615Data sources: Bielefeld Academic Search Engine (BASE)Queen Mary University of London: Queen Mary Research Online (QMRO)Article . 2018License: CC BYData sources: Bielefeld Academic Search Engine (BASE)add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.molmet.2017.08.006&type=result"></script>'); --> </script>For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Other literature type , Journal 2017Embargo end date: 24 Jan 2018 Australia, Australia, United KingdomPublisher:Elsevier BV Funded by:WT, UKRI | Neurobehavioural genetics..., WT | Molecular and neural basi... +1 projectsWT ,UKRI| Neurobehavioural genetics. Isolation and characterisation of behavioural mutations in mice ,WT| Molecular and neural basis of obesity ,UKRI| Genetics of Type 2 DiabetesAdrienne E. Sullivan; I. Sadaf Farooqi; Susan Kirsch; Roger D. Cox; Cheryl L. Scudamore; Stephen O'Rahilly; Elizabeth Bentley; Patrick M. Nolan; Rasneer Sonia Bains; Inês Barroso; Elana Henning; Julia M. Keogh; Gareth Banks; Rebecca Dumbell; David C. Bersten; Murray L. Whitelaw; Murray L. Whitelaw; Michelle Simon; Lee Moir; Audrey E. Hendricks; Audrey E. Hendricks; Elena G. Bochukova; Elena G. Bochukova; Kimberly A. Watson;OBJECTIVE: Genetic studies in obese rodents and humans can provide novel insights into the mechanisms involved in energy homeostasis. METHODS: In this study, we genetically mapped the chromosomal region underlying the development of severe obesity in a mouse line identified as part of a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis screen. We characterized the metabolic and behavioral phenotype of obese mutant mice and examined changes in hypothalamic gene expression. In humans, we examined genetic data from people with severe early onset obesity. RESULTS: We identified an obese mouse heterozygous for a missense mutation (pR108W) in orthopedia homeobox (Otp), a homeodomain containing transcription factor required for the development of neuroendocrine cell lineages in the hypothalamus, a region of the brain important in the regulation of energy homeostasis. OtpR108W/+ mice exhibit increased food intake, weight gain, and anxiety when in novel environments or singly housed, phenotypes that may be partially explained by reduced hypothalamic expression of oxytocin and arginine vasopressin. R108W affects the highly conserved homeodomain, impairs DNA binding, and alters transcriptional activity in cells. We sequenced OTP in 2548 people with severe early-onset obesity and found a rare heterozygous loss of function variant in the homeodomain (Q153R) in a patient who also had features of attention deficit disorder. CONCLUSIONS: OTP is involved in mammalian energy homeostasis and behavior and appears to be necessary for the development of hypothalamic neural circuits. Further studies will be needed to investigate the contribution of rare variants in OTP to human energy homeostasis.
CORE arrow_drop_down Central Archive at the University of ReadingArticle . 2017License: CC BYData sources: CORE (RIOXX-UK Aggregator)CORE (RIOXX-UK Aggregator)Article . 2017License: http://llr.ntu.ac.uk/irep/reuseData sources: CORE (RIOXX-UK Aggregator)The University of Adelaide: Digital LibraryArticle . 2017License: CC BYFull-Text: http://hdl.handle.net/2440/129615Data sources: Bielefeld Academic Search Engine (BASE)Queen Mary University of London: Queen Mary Research Online (QMRO)Article . 2018License: CC BYData sources: Bielefeld Academic Search Engine (BASE)add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.molmet.2017.08.006&type=result"></script>'); --> </script>For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 16 citations 16 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert CORE arrow_drop_down Central Archive at the University of ReadingArticle . 2017License: CC BYData sources: CORE (RIOXX-UK Aggregator)CORE (RIOXX-UK Aggregator)Article . 2017License: http://llr.ntu.ac.uk/irep/reuseData sources: CORE (RIOXX-UK Aggregator)The University of Adelaide: Digital LibraryArticle . 2017License: CC BYFull-Text: http://hdl.handle.net/2440/129615Data sources: Bielefeld Academic Search Engine (BASE)Queen Mary University of London: Queen Mary Research Online (QMRO)Article . 2018License: CC BYData sources: Bielefeld Academic Search Engine (BASE)add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1016/j.molmet.2017.08.006&type=result"></script>'); --> </script>For further information contact us at helpdesk@openaire.eu