Mammary glands of adipophilin-null mice produce an amino-terminally truncated form of adipophilin that mediates milk lipid droplet formation and secretion.
Adipophilin (ADPH), a member of the perilipin family of lipid droplet-associated proteins, is hypothesized to mediate milk lipid formation and secretion. Unexpectedly, the fat content of milk from ADPH-null mice was only modestly lower than that of wild-type controls, and neither TIP47 nor perilipin appeared to fully compensate for ADPH loss. This prompted us to investigate the possibility that the mutated ADPH gene was not a genuine null mutation. ADPH transcripts were detected in ADPH-null mammary tissue by quantitative real-time PCR, and C-terminal-specific, but not N-terminal-specific, ADPH antibodies detected a single lower molecular weight product and immunostained cytoplasmic lipid droplets (CLDs) and secreted milk fat globules in ADPH-null mammary tissue. Furthermore, stable cell lines expressing cDNA constructs corresponding to the ADPH-null mutation produced a product comparable in size to the one detected in ADPH-null mammary glands and localized to CLDs. Based on these data, we conclude that ADPH-null mice express an N-terminally truncated form of ADPH that retains the ability to promote the formation and secretion of milk lipids.
Russell
Tanya D
TD
Graduate Program in Molecular Biology, Division of Basic Reproductive Science, University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA.
Palmer
Carol A
CA
Orlicky
David J
DJ
Bales
Elise S
ES
Chang
Benny Hung-Junn
BH
Chan
Lawrence
L
McManaman
James L
JL
D000818:Animals; D005260:Female; D007774:Lactation; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis*; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D008892:Milk / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000070780:Perilipin-2
D008055:Lipids; D008565:Membrane Proteins; D010455:Peptides; D000070780:Perilipin-2; C000602983:Plin2 protein, mouse