Peroxisome proliferator-activated receptor-binding protein null mutation results in defective mammary gland development.
A conditional null mutation of peroxisome proliferator-activated receptor-binding protein (PBP) gene was generated to understand its role in mammary gland development. PBP-deficient mammary glands exhibited retarded ductal elongation during puberty, and decreased alveolar density during pregnancy and lactation. PBP-deficient mammary glands could not produce milk to nurse pups during lactation. Both the mammary ductal elongation in response to estrogen treatment and the mammary lobuloalveolar proliferation stimulated by estrogen plus progesterone were attenuated in PBP-deficient mammary glands. The proliferation index was decreased in PBP-deficient mammary glands. PBP-deficient mammary epithelial cells expressed abundant beta-casein, whey acidic protein, and WDNM1 mRNA, indicating a relatively intact differentiated function. PBP-deficient epithelial cells were unable to form mammospheres, which were considered to be derived from mammary progenitor/stem cells. We conclude that PBP plays a pivotal role in the normal mammary gland development.
Jia
Yuzhi
Y
Department of Pathology, Northwestern University, Feinberg School of Medicine, 303 East Chicago Ave., Chicago, Illinois 60611, USA.
Qi
Chao
C
Zhang
Zhongyi
Z
Zhu
Yiwei Tony
YT
Rao
Sambasiva M
SM
Zhu
Yi-Jun
YJ
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002364:Caseins / Q000378:metabolism; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology; D004967:Estrogens / Q000378:metabolism; D005838:Genotype; D007774:Lactation; D008321:Mammary Glands, Animal / Q000196:embryology / Q000378:metabolism; D056913:Mediator Complex Subunit 1; D051379:Mice; D008894:Milk Proteins / Q000378:metabolism; D008957:Models, Genetic; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011374:Progesterone / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D019076:Transgenes
D002364:Caseins; D004967:Estrogens; C538856:Med1 protein, mouse; D056913:Mediator Complex Subunit 1; D008894:Milk Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C024471:whey acidic proteins; D011374:Progesterone; D012313:RNA; D001973:Bromodeoxyuridine