| First Author | Zhang B | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 12 | Pages | 3384-91 |
| PubMed ID | 21795745 | Mgi Jnum | J:177067 |
| Mgi Id | MGI:5293569 | Doi | 10.1182/blood-2011-05-352815 |
| Citation | Zhang B, et al. (2011) Mice deficient in LMAN1 exhibit FV and FVIII deficiencies and liver accumulation of {alpha}1-antitrypsin. Blood 118(12):3384-91 |
| abstractText | The type 1-transmembrane protein LMAN1 (ERGIC-53) forms a complex with the soluble protein MCFD2 and cycles between the endoplasmic reticulum (ER) and the ER-Golgi intermediate compartment (ERGIC). Mutations in either LMAN1 or MCFD2 cause the combined deficiency of factor V (FV) and factor VIII (FVIII; F5F8D), suggesting an ER-to-Golgi cargo receptor function for the LMAN1-MCFD2 complex. Here we report the analysis of LMAN1-deficient mice. Levels of plasma FV and FVIII, and platelet FV, are all reduced to approximately 50% of wild-type in Lman1(-/-) mice, compared with the 5%-30% levels typically observed in human F5F8D patients. Despite previous reports identifying cathepsin C, cathepsin Z, and alpha1-antitrypsin as additional potential cargoes for LMAN1, no differences were observed between wild-type and Lman1(-/-) mice in the levels of cathepsin C and cathepsin Z in liver lysates or alpha1-antitrypsin levels in plasma. LMAN1 deficiency had no apparent effect on COPII-coated vesicle formation in an in vitro assay. However, the ER in Lman1(-/-) hepatocytes is slightly distended, with significant accumulation of alpha1-antitrypsin and GRP78. An unexpected, partially penetrant, perinatal lethality was observed for Lman1(-/-) mice, dependent on the specific inbred strain genetic background, suggesting a potential role for other, as yet unidentified LMAN1-dependent cargo proteins. |
