Oocytes from the mutant restricted ovulator hen lack receptor for very low density lipoprotein

Hens of the "Restricted Ovulator" (R/O) chicken strain are characterized by the absence of egg-laying and concomitant severe hyperlipidemia due to a single gene defect (Ho, K. J., Lawrence, W. D., Lewis, L. A., Liu, L. B., and Taylor, C. B. (1974) Arch. Pathol. 98, 161-172). However, the underlying biochemical defect has not been identified. Previous studies on receptor-mediated growth of chicken oocytes have led to the characterization of a 95-kDa oocyte plasma membrane receptor that binds very low density lipoproteins (VLDL) (George, R., Barber, D. L., and Schneider, W. J. (1987) J. Biol. Chem. 262, 16838-16847). The current experiments demonstrate the absence of this receptor from R/O oocytes. Ligand binding experiments showed that ovarian membranes from mutant hens failed to display high affinity, saturable, and specific binding of 125I-VLDL. Ligand blotting with 125I-VLDL and Western blotting with polyclonal anti-receptor antibodies visualized the 95-kDa receptor in normal oocytes, but R/O ovarian membranes were devoid of any cross-reactive protein. Finally, plasma clearance of intravenously injected 125I-VLDL was dramatically impaired in R/O in comparison to normal hens, with a concomitant decrease in the radioactivity accumulating in R/O oocytes. These data strongly suggest that the absence of the 95-kDa receptor for VLDL from oocytes is responsible for the R/O phenotype, and that the receptor not only binds VLDL, but also mediates its uptake. This animal model provides a powerful tool for investigations of receptor-mediated growth of chicken oocytes and for the elucidation of regulatory mechanisms in lipid and lipoprotein metabolism of laying hens.