Analysis of Protein Phosphatase 1 Regulatory Subunit 35 (Ppp1r35) Knockout Mouse Embryos

Archambault, Danielle

Publication:
Analysis of Protein Phosphatase 1 Regulatory Subunit 35 (Ppp1r35) Knockout Mouse Embryos

dc.contributor.advisor	Jesse Mager
dc.contributor.advisor	Kimberly D. Tremblay
dc.contributor.advisor	Dominique Alfandari
dc.contributor.author	Archambault, Danielle
dc.contributor.department	University of Massachusetts Amherst
dc.contributor.department	Animal Science
dc.date	2024-03-28T20:29:52.000
dc.date.accessioned	2024-04-26T18:28:37Z
dc.date.available	2024-04-26T18:28:37Z
dc.date.issued	2020-02-01
dc.date.submitted	February
dc.date.submitted	2020
dc.description.abstract	Protein phosphatases regulate a wide array of proteins through post-translational modification and are required for a plethora of intracellular events in eukaryotes. While some core components of the protein phosphatase complexes are well characterized, many subunits of these large complexes remain unstudied. Here we characterize a murine loss-of-function allele of the protein phosphatase 1 regulatory subunit 35 (Ppp1r35) gene. Homozygous embryos lacking Ppp1r35 initiate developmental delay beginning at E7.5 and have obvious morphological defects at slightly later stages. Mutant embryos do not initiate turning and fail to progress beyond the size and relative development of an E8.5 embryo. Consistent with recent in vitro studies linking PPP1R35 with the microcephaly protein Rotatin and a role in centrosome elongation, we find that the Ppp1r35 mutant embryos lack primary cilia. Histological and molecular analysis of Ppp1r35 mutants revealed that notochord development is irregular and discontinuous and that the floor plate of the neural tube is not specified, consistent with defects in primary cilia. Similar to other mutant embryos with defects in centriole function, Ppp1r35 mutants display increased cell death that is prevalent in the neural tube and an increased number of proliferative cells in prometaphase. We hypothesize that loss of Ppp1r35 function abrogates centriole homeostasis, resulting in both a failure to produce functional primary cilia and cell death and/or cell cycle delay that leads to embryonic lethality. Taken together, these results highlight the essential function of Ppp1r35 during early mammalian development and implicate this gene as a candidate for human microcephaly.
dc.description.degree	Master of Science (M.S.)
dc.identifier.doi	https://doi.org/10.7275/6yts-rr04
dc.identifier.orcid	https://orcid.org/0000-0003-4237-7781
dc.identifier.uri	https://hdl.handle.net/20.500.14394/33934
dc.relation.url	https://scholarworks.umass.edu/cgi/viewcontent.cgi?article=1929&context=masters_theses_2&unstamped=1
dc.source.status	published
dc.subject	Life Sciences
dc.subject	Medicine and Health Sciences
dc.title	Analysis of Protein Phosphatase 1 Regulatory Subunit 35 (Ppp1r35) Knockout Mouse Embryos
dc.type	campusfive
dc.type	article
dc.type	thesis
digcom.contributor.author	isAuthorOfPublication\|email:darchambault@umass.edu\|institution:University of Massachusetts Amherst\|Archambault, Danielle
digcom.identifier	masters_theses_2/872
digcom.identifier.contextkey	16361864
digcom.identifier.submissionpath	masters_theses_2/872
dspace.entity.type	Publication