Targeted inactivation of dipeptidyl peptidase 9 enzymatic activity causes mouse neonate lethality.

Dipeptidyl Peptidase (DPP) 4 and related dipeptidyl peptidases are emerging as current and potential therapeutic targets. DPP9 is an intracellular protease that is regulated by redox status and by SUMO1. DPP9 can influence antigen processing, epidermal growth factor (EGF)-mediated signaling and tumo...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Margaret G Gall, Yiqian Chen, Ana Julia Vieira de Ribeiro, Hui Zhang, Charles G Bailey, Derek S Spielman, Denise M T Yu, Mark D Gorrell
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a53568362b3e4e698b1e39e9eef2c700
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a53568362b3e4e698b1e39e9eef2c700
record_format	dspace
spelling	oai:doaj.org-article:a53568362b3e4e698b1e39e9eef2c7002021-11-18T08:48:08ZTargeted inactivation of dipeptidyl peptidase 9 enzymatic activity causes mouse neonate lethality.1932-620310.1371/journal.pone.0078378https://doaj.org/article/a53568362b3e4e698b1e39e9eef2c7002013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24223149/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Dipeptidyl Peptidase (DPP) 4 and related dipeptidyl peptidases are emerging as current and potential therapeutic targets. DPP9 is an intracellular protease that is regulated by redox status and by SUMO1. DPP9 can influence antigen processing, epidermal growth factor (EGF)-mediated signaling and tumor biology. We made the first gene knock-in (gki) mouse with a serine to alanine point mutation at the DPP9 active site (S729A). Weaned heterozygote DPP9 (wt/S729A) pups from 110 intercrosses were indistinguishable from wild-type littermates. No homozygote DPP9 (S729A/S729A) weaned mice were detected. DPP9 (S729A/S729A) homozygote embryos, which were morphologically indistinguishable from their wild-type littermate embryos at embryonic day (ED) 12.5 to ED 17.5, were born live but these neonates died within 8 to 24 hours of birth. All neonates suckled and contained milk spots and were of similar body weight. No gender differences were seen. No histological or DPP9 immunostaining pattern differences were seen between genotypes in embryos and neonates. Mouse embryonic fibroblasts (MEFs) from DPP9 (S729A/S729A) ED13.5 embryos and neonate DPP9 (S729A/S729A) mouse livers collected within 6 hours after birth had levels of DPP9 protein and DPP9-related proteases that were similar to wild-type but had less DPP9/DPP8-derived activity. These data confirmed the absence of DPP9 enzymatic activity due to the presence of the serine to alanine mutation and no compensation from related proteases. These novel findings suggest that DPP9 enzymatic activity is essential for early neonatal survival in mice.Margaret G GallYiqian ChenAna Julia Vieira de RibeiroHui ZhangCharles G BaileyDerek S SpielmanDenise M T YuMark D GorrellPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e78378 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Margaret G Gall Yiqian Chen Ana Julia Vieira de Ribeiro Hui Zhang Charles G Bailey Derek S Spielman Denise M T Yu Mark D Gorrell Targeted inactivation of dipeptidyl peptidase 9 enzymatic activity causes mouse neonate lethality.
description	Dipeptidyl Peptidase (DPP) 4 and related dipeptidyl peptidases are emerging as current and potential therapeutic targets. DPP9 is an intracellular protease that is regulated by redox status and by SUMO1. DPP9 can influence antigen processing, epidermal growth factor (EGF)-mediated signaling and tumor biology. We made the first gene knock-in (gki) mouse with a serine to alanine point mutation at the DPP9 active site (S729A). Weaned heterozygote DPP9 (wt/S729A) pups from 110 intercrosses were indistinguishable from wild-type littermates. No homozygote DPP9 (S729A/S729A) weaned mice were detected. DPP9 (S729A/S729A) homozygote embryos, which were morphologically indistinguishable from their wild-type littermate embryos at embryonic day (ED) 12.5 to ED 17.5, were born live but these neonates died within 8 to 24 hours of birth. All neonates suckled and contained milk spots and were of similar body weight. No gender differences were seen. No histological or DPP9 immunostaining pattern differences were seen between genotypes in embryos and neonates. Mouse embryonic fibroblasts (MEFs) from DPP9 (S729A/S729A) ED13.5 embryos and neonate DPP9 (S729A/S729A) mouse livers collected within 6 hours after birth had levels of DPP9 protein and DPP9-related proteases that were similar to wild-type but had less DPP9/DPP8-derived activity. These data confirmed the absence of DPP9 enzymatic activity due to the presence of the serine to alanine mutation and no compensation from related proteases. These novel findings suggest that DPP9 enzymatic activity is essential for early neonatal survival in mice.
format	article
author	Margaret G Gall Yiqian Chen Ana Julia Vieira de Ribeiro Hui Zhang Charles G Bailey Derek S Spielman Denise M T Yu Mark D Gorrell
author_facet	Margaret G Gall Yiqian Chen Ana Julia Vieira de Ribeiro Hui Zhang Charles G Bailey Derek S Spielman Denise M T Yu Mark D Gorrell
author_sort	Margaret G Gall
title	Targeted inactivation of dipeptidyl peptidase 9 enzymatic activity causes mouse neonate lethality.
title_short	Targeted inactivation of dipeptidyl peptidase 9 enzymatic activity causes mouse neonate lethality.
title_full	Targeted inactivation of dipeptidyl peptidase 9 enzymatic activity causes mouse neonate lethality.
title_fullStr	Targeted inactivation of dipeptidyl peptidase 9 enzymatic activity causes mouse neonate lethality.
title_full_unstemmed	Targeted inactivation of dipeptidyl peptidase 9 enzymatic activity causes mouse neonate lethality.
title_sort	targeted inactivation of dipeptidyl peptidase 9 enzymatic activity causes mouse neonate lethality.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a53568362b3e4e698b1e39e9eef2c700
work_keys_str_mv	AT margaretggall targetedinactivationofdipeptidylpeptidase9enzymaticactivitycausesmouseneonatelethality AT yiqianchen targetedinactivationofdipeptidylpeptidase9enzymaticactivitycausesmouseneonatelethality AT anajuliavieiraderibeiro targetedinactivationofdipeptidylpeptidase9enzymaticactivitycausesmouseneonatelethality AT huizhang targetedinactivationofdipeptidylpeptidase9enzymaticactivitycausesmouseneonatelethality AT charlesgbailey targetedinactivationofdipeptidylpeptidase9enzymaticactivitycausesmouseneonatelethality AT dereksspielman targetedinactivationofdipeptidylpeptidase9enzymaticactivitycausesmouseneonatelethality AT denisemtyu targetedinactivationofdipeptidylpeptidase9enzymaticactivitycausesmouseneonatelethality AT markdgorrell targetedinactivationofdipeptidylpeptidase9enzymaticactivitycausesmouseneonatelethality
_version_	1718421278987124736

Targeted inactivation of dipeptidyl peptidase 9 enzymatic activity causes mouse neonate lethality.

Ejemplares similares