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Generation of Conditional Knockout Alleles for PRUNE-1
PRUNE1 is a member of the aspartic acid-histidine-histidine (DHH) protein superfamily, which could display an exopolyphosphatase activity and interact with multiple cellular proteins involved in the cytoskeletal rearrangement. It is widely expressed during embryonic development and is essential for...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954577/ https://www.ncbi.nlm.nih.gov/pubmed/36831191 http://dx.doi.org/10.3390/cells12040524 |
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author | Wu, Xiaoli Simard, Louise R. Ding, Hao |
author_facet | Wu, Xiaoli Simard, Louise R. Ding, Hao |
author_sort | Wu, Xiaoli |
collection | PubMed |
description | PRUNE1 is a member of the aspartic acid-histidine-histidine (DHH) protein superfamily, which could display an exopolyphosphatase activity and interact with multiple cellular proteins involved in the cytoskeletal rearrangement. It is widely expressed during embryonic development and is essential for embryogenesis. PRUNE1 could also be critical for postnatal development of the nervous system as it was found to be mutated in patients with microcephaly, brain malformations, and neurodegeneration. To determine the cellular function of PRUNE1 during development and in disease, we have generated conditional mouse alleles of the Prune1 in which loxP sites flank exon 6. Crossing these alleles with a ubiquitous Cre transgenic line resulted in a complete loss of PRUNE1 expression and embryonic defects identical to those previously described for Prune1 null embryos. In addition, breeding these alleles with a Purkinje cell-specific Cre line (Pcp2-Cre) resulted in the loss of Purkinje cells similar to that observed in patients carrying a mutation with loss of PRUNE1 function. Therefore, the Prune1 conditional mouse alleles generated in this study provide important genetic tools not only for dissecting the spatial and temporal roles of PRUNE1 during development but also for understanding the pathogenic role of PRUNE1 dysfunction in neurodegenerative or neurodevelopmental disease. In addition, from this work, we have described an approach that allows one to efficiently generate conditional mouse alleles based on mouse zygote electroporation. |
format | Online Article Text |
id | pubmed-9954577 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99545772023-02-25 Generation of Conditional Knockout Alleles for PRUNE-1 Wu, Xiaoli Simard, Louise R. Ding, Hao Cells Communication PRUNE1 is a member of the aspartic acid-histidine-histidine (DHH) protein superfamily, which could display an exopolyphosphatase activity and interact with multiple cellular proteins involved in the cytoskeletal rearrangement. It is widely expressed during embryonic development and is essential for embryogenesis. PRUNE1 could also be critical for postnatal development of the nervous system as it was found to be mutated in patients with microcephaly, brain malformations, and neurodegeneration. To determine the cellular function of PRUNE1 during development and in disease, we have generated conditional mouse alleles of the Prune1 in which loxP sites flank exon 6. Crossing these alleles with a ubiquitous Cre transgenic line resulted in a complete loss of PRUNE1 expression and embryonic defects identical to those previously described for Prune1 null embryos. In addition, breeding these alleles with a Purkinje cell-specific Cre line (Pcp2-Cre) resulted in the loss of Purkinje cells similar to that observed in patients carrying a mutation with loss of PRUNE1 function. Therefore, the Prune1 conditional mouse alleles generated in this study provide important genetic tools not only for dissecting the spatial and temporal roles of PRUNE1 during development but also for understanding the pathogenic role of PRUNE1 dysfunction in neurodegenerative or neurodevelopmental disease. In addition, from this work, we have described an approach that allows one to efficiently generate conditional mouse alleles based on mouse zygote electroporation. MDPI 2023-02-06 /pmc/articles/PMC9954577/ /pubmed/36831191 http://dx.doi.org/10.3390/cells12040524 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Wu, Xiaoli Simard, Louise R. Ding, Hao Generation of Conditional Knockout Alleles for PRUNE-1 |
title | Generation of Conditional Knockout Alleles for PRUNE-1 |
title_full | Generation of Conditional Knockout Alleles for PRUNE-1 |
title_fullStr | Generation of Conditional Knockout Alleles for PRUNE-1 |
title_full_unstemmed | Generation of Conditional Knockout Alleles for PRUNE-1 |
title_short | Generation of Conditional Knockout Alleles for PRUNE-1 |
title_sort | generation of conditional knockout alleles for prune-1 |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954577/ https://www.ncbi.nlm.nih.gov/pubmed/36831191 http://dx.doi.org/10.3390/cells12040524 |
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