Cargando…
Holocarboxylase synthetase knockout is embryonic lethal in mice
Holocarboxylase synthetase (HLCS) catalyzes the biotinylation of five distinct biotin-dependent carboxylases and perhaps chromatin proteins. HLCS deficiency causes multiple carboxylase deficiency which results in fatal consequences unless patients are diagnosed early and treated with pharmacological...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985998/ https://www.ncbi.nlm.nih.gov/pubmed/35385533 http://dx.doi.org/10.1371/journal.pone.0265539 |
_version_ | 1784682461026844672 |
---|---|
author | Sadri, Mahrou Wang, Haichuan Kuroishi, Toshinobu Li, Yong Zempleni, Janos |
author_facet | Sadri, Mahrou Wang, Haichuan Kuroishi, Toshinobu Li, Yong Zempleni, Janos |
author_sort | Sadri, Mahrou |
collection | PubMed |
description | Holocarboxylase synthetase (HLCS) catalyzes the biotinylation of five distinct biotin-dependent carboxylases and perhaps chromatin proteins. HLCS deficiency causes multiple carboxylase deficiency which results in fatal consequences unless patients are diagnosed early and treated with pharmacological doses of biotin. The objective of this study was to develop an HLCS conditional knockout (KO) mouse and assess effects of HLCS knockout on embryo survival. In the mouse, exon 8 is flanked by LoxP sites, thereby removing a catalytically important region upon recombination by Cre. HLCS conditional KO mice were backcrossed for 14 generations with C57BL/6J mice to yield Hlcs(tm1Jze). Fertility and weight gain were normal and no frank disease phenotypes and abnormal feeding behavior were observed in the absence of Cre. HLCS knockout was embryonic lethal when dams homozygous for both the floxed Hlcs gene and tamoxifen-inducible Cre recombinase (denoted Hlcs(tm1.1Jze)) were injected with tamoxifen on gestational days 2.5 and 10.5. This is the first report of an HLCS conditional KO mouse, which enables studies of the roles of HLCS and biotin in intermediary metabolism. |
format | Online Article Text |
id | pubmed-8985998 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-89859982022-04-07 Holocarboxylase synthetase knockout is embryonic lethal in mice Sadri, Mahrou Wang, Haichuan Kuroishi, Toshinobu Li, Yong Zempleni, Janos PLoS One Research Article Holocarboxylase synthetase (HLCS) catalyzes the biotinylation of five distinct biotin-dependent carboxylases and perhaps chromatin proteins. HLCS deficiency causes multiple carboxylase deficiency which results in fatal consequences unless patients are diagnosed early and treated with pharmacological doses of biotin. The objective of this study was to develop an HLCS conditional knockout (KO) mouse and assess effects of HLCS knockout on embryo survival. In the mouse, exon 8 is flanked by LoxP sites, thereby removing a catalytically important region upon recombination by Cre. HLCS conditional KO mice were backcrossed for 14 generations with C57BL/6J mice to yield Hlcs(tm1Jze). Fertility and weight gain were normal and no frank disease phenotypes and abnormal feeding behavior were observed in the absence of Cre. HLCS knockout was embryonic lethal when dams homozygous for both the floxed Hlcs gene and tamoxifen-inducible Cre recombinase (denoted Hlcs(tm1.1Jze)) were injected with tamoxifen on gestational days 2.5 and 10.5. This is the first report of an HLCS conditional KO mouse, which enables studies of the roles of HLCS and biotin in intermediary metabolism. Public Library of Science 2022-04-06 /pmc/articles/PMC8985998/ /pubmed/35385533 http://dx.doi.org/10.1371/journal.pone.0265539 Text en © 2022 Sadri et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Sadri, Mahrou Wang, Haichuan Kuroishi, Toshinobu Li, Yong Zempleni, Janos Holocarboxylase synthetase knockout is embryonic lethal in mice |
title | Holocarboxylase synthetase knockout is embryonic lethal in mice |
title_full | Holocarboxylase synthetase knockout is embryonic lethal in mice |
title_fullStr | Holocarboxylase synthetase knockout is embryonic lethal in mice |
title_full_unstemmed | Holocarboxylase synthetase knockout is embryonic lethal in mice |
title_short | Holocarboxylase synthetase knockout is embryonic lethal in mice |
title_sort | holocarboxylase synthetase knockout is embryonic lethal in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985998/ https://www.ncbi.nlm.nih.gov/pubmed/35385533 http://dx.doi.org/10.1371/journal.pone.0265539 |
work_keys_str_mv | AT sadrimahrou holocarboxylasesynthetaseknockoutisembryoniclethalinmice AT wanghaichuan holocarboxylasesynthetaseknockoutisembryoniclethalinmice AT kuroishitoshinobu holocarboxylasesynthetaseknockoutisembryoniclethalinmice AT liyong holocarboxylasesynthetaseknockoutisembryoniclethalinmice AT zemplenijanos holocarboxylasesynthetaseknockoutisembryoniclethalinmice |