title: Differential requirement of GRP94 and GRP78 in mammary gland development.
abstract: Glucose Regulated Protein (GRP) 94 and GRP78 are critical molecular chaperones and regulators of signaling. Conditional knockout mouse models have revealed tissue specific requirements for GRP94 and GRP78, including selection for allele retention in specific cell types. Here we report the consequences of mammary-targeted knockout of these GRPs. Our studies revealed that MMTV-Cre, Grp94(f/f) mammary glands, despite GRP94 deficiency, exhibited normal proliferation and ductal morphogenesis. Interestingly, MMTV-Cre, Grp78(f/f) mammary glands displayed only slightly reduced GRP78 protein levels, associating with the retention of the non-recombined Grp78 floxed alleles in isolated mammary epithelial cells and displayed phenotypes comparable to wild-type glands. In contrast, transduction of isolated Grp78(f/f) mammary epithelial stem/progenitor cells with adenovirus expressing GFP and Cre-recombinase was successful in GRP78 ablation, and the GFP sorted cells failed to give rise to repopulated mammary glands in de-epithelialized recipient mice. These studies imply GRP78, but not GRP94, is required for mammary gland development.
authors: Department of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors: Genyuan
authors: G
authors: Zhu
authors: 1] Department of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA [2].
authors: Miao
authors: M
authors: Wang
authors: Gene Expression Laboratories, The Salk Institute for Biological Studies, La Jolla, CA, USA.
authors: Benjamin
authors: B
authors: Spike
authors: Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA, USA.
authors: Peter C
authors: PC
authors: Gray
authors: Department of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors: Jieli
authors: J
authors: Shen
authors: Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
authors: Sung-Hyung
authors: SH
authors: Lee
authors: Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
authors: Si-Yi
authors: SY
authors: Chen
authors: Department of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors: Amy S
authors: AS
authors: Lee
mesh_terms: D000818:Animals; D000091342:Endoplasmic Reticulum Chaperone BiP; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; C053387:endoplasmin