Generation of a Transgenic Mouse Model for Investigating Mitochondria in Sperm

Mitochondria play a crucial role in sperm development; however, the mechanisms regulating their function in sperm remain poorly understood. Developing a method to regulate the expression of a target gene within the mitochondria of sperm is a vital step in this area of research. In this study, we aim...

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Main Authors: Hironmoy Sarkar, Suryaprakash R. Batta, Neerja Wadhwa, Subeer S. Majumdar, Bhola Shankar Pradhan
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/4/296
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author Hironmoy Sarkar
Suryaprakash R. Batta
Neerja Wadhwa
Subeer S. Majumdar
Bhola Shankar Pradhan
author_facet Hironmoy Sarkar
Suryaprakash R. Batta
Neerja Wadhwa
Subeer S. Majumdar
Bhola Shankar Pradhan
author_sort Hironmoy Sarkar
collection DOAJ
description Mitochondria play a crucial role in sperm development; however, the mechanisms regulating their function in sperm remain poorly understood. Developing a method to regulate the expression of a target gene within the mitochondria of sperm is a vital step in this area of research. In this study, we aimed to create a system for expressing a transgene in the mitochondria of sperm. As a proof of concept, we generated transgenic mice that express green fluorescent protein (GFP) fused with a mitochondrial localization signal (MLS) driven by the phosphoglycerate kinase 2 (PGK2) promoter, which facilitates the transgene expression in the sperm. Although the PGK2 promoter has previously shown to drive gene expression in spermatocytes and spermatids, the novelty of our approach lies in the combination of PGK2-driven MLS-GFP expression to study mitochondria in vivo. We established two founder lines of transgenic mice through pronuclear microinjection, and MLS-GFP expression was confirmed in the mitochondria of sperm cells using fluorescence microscopy and flow cytometry. Consequently, we provide a novel platform for investigating mitochondrial function in sperm, where GFP can be substituted with other genes of interest to examine their effects on mitochondria. This system specifically targets sperm mitochondria, offering an innovative approach for studying mitochondrial function in vivo.
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spelling doaj-art-6f1d170130954d69974da7fa396d8d5c2025-08-20T03:12:14ZengMDPI AGCells2073-44092025-02-0114429610.3390/cells14040296Generation of a Transgenic Mouse Model for Investigating Mitochondria in SpermHironmoy Sarkar0Suryaprakash R. Batta1Neerja Wadhwa2Subeer S. Majumdar3Bhola Shankar Pradhan4Cellular Endocrinology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, JNU Complex, New Delhi 110067, IndiaCellular Endocrinology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, JNU Complex, New Delhi 110067, IndiaEmbryo Biotechnology Lab, National Institute of Immunology, New Delhi 110067, IndiaCellular Endocrinology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, JNU Complex, New Delhi 110067, IndiaCellular Endocrinology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, JNU Complex, New Delhi 110067, IndiaMitochondria play a crucial role in sperm development; however, the mechanisms regulating their function in sperm remain poorly understood. Developing a method to regulate the expression of a target gene within the mitochondria of sperm is a vital step in this area of research. In this study, we aimed to create a system for expressing a transgene in the mitochondria of sperm. As a proof of concept, we generated transgenic mice that express green fluorescent protein (GFP) fused with a mitochondrial localization signal (MLS) driven by the phosphoglycerate kinase 2 (PGK2) promoter, which facilitates the transgene expression in the sperm. Although the PGK2 promoter has previously shown to drive gene expression in spermatocytes and spermatids, the novelty of our approach lies in the combination of PGK2-driven MLS-GFP expression to study mitochondria in vivo. We established two founder lines of transgenic mice through pronuclear microinjection, and MLS-GFP expression was confirmed in the mitochondria of sperm cells using fluorescence microscopy and flow cytometry. Consequently, we provide a novel platform for investigating mitochondrial function in sperm, where GFP can be substituted with other genes of interest to examine their effects on mitochondria. This system specifically targets sperm mitochondria, offering an innovative approach for studying mitochondrial function in vivo.https://www.mdpi.com/2073-4409/14/4/296mitochondriaPGK2MLSspermtransgenic mice
spellingShingle Hironmoy Sarkar
Suryaprakash R. Batta
Neerja Wadhwa
Subeer S. Majumdar
Bhola Shankar Pradhan
Generation of a Transgenic Mouse Model for Investigating Mitochondria in Sperm
Cells
mitochondria
PGK2
MLS
sperm
transgenic mice
title Generation of a Transgenic Mouse Model for Investigating Mitochondria in Sperm
title_full Generation of a Transgenic Mouse Model for Investigating Mitochondria in Sperm
title_fullStr Generation of a Transgenic Mouse Model for Investigating Mitochondria in Sperm
title_full_unstemmed Generation of a Transgenic Mouse Model for Investigating Mitochondria in Sperm
title_short Generation of a Transgenic Mouse Model for Investigating Mitochondria in Sperm
title_sort generation of a transgenic mouse model for investigating mitochondria in sperm
topic mitochondria
PGK2
MLS
sperm
transgenic mice
url https://www.mdpi.com/2073-4409/14/4/296
work_keys_str_mv AT hironmoysarkar generationofatransgenicmousemodelforinvestigatingmitochondriainsperm
AT suryaprakashrbatta generationofatransgenicmousemodelforinvestigatingmitochondriainsperm
AT neerjawadhwa generationofatransgenicmousemodelforinvestigatingmitochondriainsperm
AT subeersmajumdar generationofatransgenicmousemodelforinvestigatingmitochondriainsperm
AT bholashankarpradhan generationofatransgenicmousemodelforinvestigatingmitochondriainsperm