Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Xiaoli, Simard, Louise R., Ding, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1784894151483981824
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
work_keys_str_mv AT wuxiaoli generationofconditionalknockoutallelesforprune1
AT simardlouiser generationofconditionalknockoutallelesforprune1
AT dinghao generationofconditionalknockoutallelesforprune1