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Holocarboxylase synthetase knockout is embryonic lethal in mice
Mahrou Sadri1, Haichuan Wang1, Toshinobu Kuroishi1
1Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
Plos One
|April 6, 2022
Summary
Holocarboxylase synthetase (HLCS) deficiency causes fatal multiple carboxylase deficiency. This study developed a conditional knockout mouse, revealing HLCS knockout is embryonic lethal, highlighting biotin's crucial role in development.
Area of Science:
- Biochemistry
- Genetics
- Developmental Biology
Background:
- Holocarboxylase synthetase (HLCS) is vital for biotinylating carboxylases and chromatin proteins.
- HLCS deficiency leads to multiple carboxylase deficiency, a severe condition requiring early biotin treatment.
- Understanding HLCS function is critical for metabolic and developmental studies.
Purpose of the Study:
- To develop a conditional knockout (KO) mouse model for Holocarboxylase synthetase (HLCS).
- To investigate the impact of HLCS knockout on embryonic survival and development.
- To establish a tool for studying HLCS and biotin roles in intermediary metabolism.
Main Methods:
- Generated a conditional HLCS knockout mouse by flanking exon 8 with LoxP sites.
- Utilized tamoxifen-inducible Cre recombinase for targeted HLCS gene deletion.
- Administered tamoxifen to pregnant dams at specific gestational stages to induce knockout.
Main Results:
- HLCS conditional KO mice (Hlcstm1Jze) showed normal fertility, weight, and no overt phenotypes without Cre.
- Embryonic lethality was observed in HLCS knockout mice (Hlcstm1.1Jze) following tamoxifen induction.
- This confirms HLCS is essential for embryonic survival.
Conclusions:
- The developed HLCS conditional KO mouse is a valuable model for studying biotin metabolism.
- HLCS is indispensable for embryonic development, likely due to its role in biotin-dependent carboxylases.
- This model opens avenues for research into metabolic disorders and biotin's physiological functions.
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