Disruption of Iqsec1 in mice leads to embryonic lethality with reduced large apical vacuoles in the visceral endoderm

Iqsec1 (IQ motif and Sec7 domain-containing protein 1), also known as BRAG2 (Brefeldin A-resistant Arf-GEF 2), is a guanine nucleotide exchange factor that regulates membrane trafficking, cytoskeletal organization, and signal transduction by activating class II and III ADP-ribosylation factors. To i...

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Veröffentlicht in:FEBS letters 2024-11
Hauptverfasser: Sakagami, Hiroyuki, Shiroshima, Tomoko, Nemoto, Noriko, Niimura, Tomoko, Sugawara, Takeyuki, Hara, Yoshinobu, Saito, Koji, Okubo, Tadashi, Fukaya, Masahiro
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container_title FEBS letters
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creator Sakagami, Hiroyuki
Shiroshima, Tomoko
Nemoto, Noriko
Niimura, Tomoko
Sugawara, Takeyuki
Hara, Yoshinobu
Saito, Koji
Okubo, Tadashi
Fukaya, Masahiro
description Iqsec1 (IQ motif and Sec7 domain-containing protein 1), also known as BRAG2 (Brefeldin A-resistant Arf-GEF 2), is a guanine nucleotide exchange factor that regulates membrane trafficking, cytoskeletal organization, and signal transduction by activating class II and III ADP-ribosylation factors. To investigate the physiological role of Iqsec1 at the whole animal level, we generated Iqsec1-deficient mice using CRISPR/Cas9-mediated gene editing. Nearly all Iqsec1 mice (99%) exhibited embryonic lethality with severe growth retardation. Electron microscopy revealed that Iqsec1 embryos at embryonic day 8.5 lacked large apical vacuoles in visceral endoderm cells of the yolk sac, compared with controls. These findings suggest that Iqsec1 plays a critical role in embryogenesis, likely through regulation of membrane trafficking in visceral endoderm cells.
doi_str_mv 10.1002/1873-3468.15058
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title Disruption of Iqsec1 in mice leads to embryonic lethality with reduced large apical vacuoles in the visceral endoderm
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