Murine SEC24D can substitute functionally for SEC24C during embryonic development

AbstractThe COPII component SEC24 mediates the recruitment of transmembrane cargos or cargo adaptors into newly forming COPII vesicles on the ER membrane. Mammalian genomes encode four Sec24 paralogs (Sec24a-d), with two subfamilies based on sequence homology (SEC24A/B and C/D), though little is known about their comparative functions and cargo-specificities. Complete deficiency for Sec24d results in very early embryonic lethality in mice (before the 8 cell stage), with later embryonic lethality (E7.5) observed in Sec24c null mice. To test the potential overlap in function between SEC24C/D, we employed dual recombinase mediated cassette exchange to generate a Sec24cc-d allele, in which the C-terminal 90% of SEC24C has been replaced by SEC24D coding sequence. In contrast to the embryonic lethality at E7.5 of SEC24C-deficiency, Sec24cc-d/c-d pups survive to term, though dying shortly after birth. Sec24cc-d/c-d pups are smaller in size, but exhibit no other obvious developmental abnormality by pathologic evaluation. These results suggest that tissue-specific and/or stage-specific expression of the Sec24c/d genes rather than differences in cargo export function explain the early embryonic requirements for SEC24C and SEC24D.

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Murine SEC24D Can Substitute Functionally for SEC24Cin vivo

10.1101/284398 ◽

2018 ◽

Cited By ~ 2

Author(s):

Elizabeth J. Adams ◽

Rami Khoriaty ◽

Anna Kiseleva ◽

Audrey C. A. Cleuren ◽

Kärt Tomberg ◽

...

Keyword(s):

Sequence Homology ◽

Embryonic Lethality ◽

Developmental Abnormality ◽

Cell Stage ◽

Specific Expression ◽

Coding Sequence ◽

Cassette Exchange ◽

Early Embryonic Lethality ◽

Mammalian Genomes ◽

Copii Vesicles

ABSTRACTThe COPII component SEC24 mediates the recruitment of transmembrane cargoes or cargo adaptors into newly forming COPII vesicles on the ER membrane. Mammalian genomes encode fourSec24paralogs (Sec24a-d), with two subfamilies based on sequence homology (SEC24A/B and C/D), though little is known about their comparative functions and cargo-specificities. Complete deficiency forSec24dresults in very early embryonic lethality in mice (before the 8 cell stage), with later embryonic lethality (E 7.5) observed inSec24cnull mice. To test the potential overlap in function between SEC24C/D, we employed dual recombinase mediated cassette exchange to generate aSec24cc-dallele, in which the C-terminal 90% of SEC24C has been replaced by SEC24D coding sequence. In contrast to the embryonic lethality at E7.5 of SEC24C-deficiency,Sec24cc-d/c-dpups survive to term, though dying shortly after birth.Sec24cc-d/c-dpups are smaller in size, but exhibit no obvious developmental abnormality. These results suggest that tissue-specific and/or stage-specific expression of theSec24c/dgenes rather than differences in cargo function explain the early embryonic requirements for SEC24C and SEC24D.

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Faculty Opinions recommendation of Targeted disruption of the Nijmegen breakage syndrome gene NBS1 leads to early embryonic lethality in mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.12111957.13261054 ◽

2011 ◽

Author(s):

Patrick C Wilson

Keyword(s):

Nijmegen Breakage Syndrome ◽

Embryonic Lethality ◽

Targeted Disruption ◽

Early Embryonic Lethality

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Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3

Nature Communications ◽

10.1038/s41467-021-23510-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Laura Santini ◽

Florian Halbritter ◽

Fabian Titz-Teixeira ◽

Toru Suzuki ◽

Maki Asami ◽

...

Keyword(s):

Bisulfite Sequencing ◽

Blastocyst Stage ◽

Preimplantation Embryos ◽

Imprinted Genes ◽

Specific Expression ◽

Histone 3 ◽

Complex Program ◽

Genome Bisulfite Sequencing ◽

Mammalian Genomes ◽

Parent Of Origin

AbstractIn mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation.

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Loss of Pnn expression results in mouse early embryonic lethality and cellular apoptosis through SRSF1-mediated alternative expression of Bcl-xS and ICAD

Journal of Cell Science ◽

10.1242/jcs.100859 ◽

2012 ◽

Vol 125 (13) ◽

pp. 3164-3172 ◽

Cited By ~ 19

Author(s):

Steve Leu ◽

Yen-Ming Lin ◽

Chu-Han Wu ◽

Pin Ouyang

Keyword(s):

Embryonic Lethality ◽

Early Embryonic Lethality ◽

Alternative Expression ◽

Cellular Apoptosis

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Deficiency of lysyl hydroxylase 2 in mice causes systemic endoplasmic reticulum stress leading to early embryonic lethality

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2019.03.091 ◽

2019 ◽

Vol 512 (3) ◽

pp. 486-491 ◽

Cited By ~ 2

Author(s):

Atsushi Kasamatsu ◽

Katsuhiro Uzawa ◽

Fumihiko Hayashi ◽

Akihiro Kita ◽

Yasuhiko Okubo ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Embryonic Lethality ◽

Lysyl Hydroxylase ◽

Early Embryonic Lethality

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Rescue of Prothrombin-deficiency by Transgene Expression in Mice

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613344 ◽

2002 ◽

Vol 88 (12) ◽

pp. 984-991 ◽

Cited By ~ 20

Author(s):

William Sun ◽

Mallory Coleman ◽

David Witte ◽

Sandra Degen

Keyword(s):

Transgenic Mice ◽

Transgene Expression ◽

Embryonic Lethality ◽

The Other ◽

Model Systems ◽

Bleeding Events ◽

Specific Expression ◽

Spontaneous Bleeding ◽

Knock Out ◽

Transgenic Expression

SummaryProthrombin has diverse biological functions in addition to its well established role in blood coagulation. In order to study these functions in more detail mouse model systems are needed. Since deficiency of prothrombin in mice results in partial embryonic lethality and neonatal death, alternative approaches are required to study the biology of prothrombin in the adult mouse. The liver is the major site of synthesis of prothrombin and therefore liver-specific promoters were used to express prothrombin in transgenic mice. Mice generated from crosses with these transgenic mice and mice hemizygous for the knock-out allele were used to test whether liver-specific expression is sufficient to correct the phenotype of null mice and whether liver-specific expression is sufficient for the development and survival of mice to adulthood. The mouse albumin promoter/enhancer was used initially for transgene expression without success in obtaining transgene positive, endogenous prothrombin null mice. Two lines of transgene positive, endogenous prothrombin deficient mice were obtained using the mouse transthyretin (TTR) promoter/enhancer driving expression of a human prothrombin cDNA. One line was able to rescue both the embryonic and the neonatal lethality while the other line was only able to correct the embryonic lethality. Expression of prothrombin was restricted to the liver and stomach in one line and to the liver, pancreas, stomach and kidney in the other line of mice. Thrombin activity for one line was determined to be at 5-10% of wildtype levels. These mice developed normally and did not have spontaneous bleeding events unless traumatized. Therefore, transgenic expression of human prothrombin is sufficient for the rescue of the lethality found for prothrombin deficiency in mice.

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