PT  - JOURNAL ARTICLE
AU  - Elizabeth J. Adams
AU  - Rami Khoriaty
AU  - Anna Kiseleva
AU  - Audrey C. A. Cleuren
AU  - Kärt Tomberg
AU  - Martijn A. van der Ent
AU  - Peter Gergics
AU  - K. Sue O’Shea
AU  - Thomas L. Saunders
AU  - David Ginsburg
TI  - Murine SEC24D Can Substitute Functionally for SEC24C <em>in vivo</em>
AID  - 10.1101/284398
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 284398
4099  - http://biorxiv.org/content/early/2018/03/22/284398.short
4100  - http://biorxiv.org/content/early/2018/03/22/284398.full
AB  - The COPII component SEC24 mediates the recruitment of transmembrane cargoes 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 (E 7.5) 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dual recombinase mediated cassette exchange to generate a Sec24cc-d allele, in which the C-terminal 90% of SEC24C has been replaced by SEC24D coding sequence.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 obvious developmental abnormality. These results suggest that tissue-specific and/or stage-specific expression of the Sec24c/d genes rather than differences in cargo function explain the early embryonic requirements for SEC24C and SEC24D.