The p24 family member p23 is required for early embryonic development

The p24 family of type I integral membrane proteins, which are localised in the endoplasmic reticulum (ER) [1-3], the intermediate compartment and the Golgi apparatus, are thought to function as receptors for cargo exit from the ER and in transport vesicle formation [4-7], Members of the p24 family have been found in a molecular complex [8,9] and are enriched in COPI-coate d vesicles, which are involved in membrane traffic between the ER and Golgi complex [1], Although expressed abundantly, simultaneous deletion of sever al family members does not appear to affect cell viability and protein secr etion in yeast [8], In order to gain more insights into the physiological r oles of different p24 proteins, we generated mice deficient in the expressi on of one family member, p23 (also called 24 delta(1), see [2] for alternat ive nomenclature). In contrast to yeast genetics, in mice disruption of bot h p23 alleles resulted in early embryonic lethality. Inactivation of one al lele led not only to reduced levels of p23 itself but also to reduced level s of other family members. The reduction in steady state protein levels als o induced structural changes in the Golgi apparatus, such as the formation of dilated saccules, The generation of mice deficient in p23 expression has revealed an essential and non-redundant role for p23 in the earliest stage s of mammalian development. It has also provided genetic evidence for the p articipation of p24 family members in oligomeric complexes and indicates a structural role for these proteins in maintaining the integrity of the earl y secretory pathway.