{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["26(18)"],"submitter":["Kim SS"],"funding":["Intramural NIH HHS"],"pubmed_abstract":["Alternative splicing in the BRCA1 locus generates multiple protein products including BRCA1-Delta11, which is identical to the BRCA1 full-length isoform (BRCA1-FL) except for the absence of exon 11. Mutation analysis using gene targeting to create null mutations or disrupt BRCA-FL has provided much of our understanding of BRCA1 functions; however, targeted mutation of specific short forms of BRCA1 has not been reported. To understand the physiologic functions of BRCA1-Delta11, we used a knock-in approach that blocks alternative splicing between exons 10 and 12 to prevent the formation of this form of BRCA1. We showed that homozygous mutant mice (Brca1(FL/FL)) were born at a Mendelian ratio without obvious developmental defects. However, the majority of Brca1(FL/FL) female mice showed mammary gland abnormalities and uterine hyperplasia after one year of age with spontaneous tumor formation. Cultured Brca1(FL/FL) cells exhibited abnormal centrosome amplification and reduction of G(1) population that was accompanied by accumulation of cyclin E and cyclin A. Accumulation of cyclin E was also found in epithelial layers of dilated ducts and hyperproliferative lobular regions in the mammary glands of Brca1(FL/FL) mice. These observations provide evidence that BRCA1 splicing variants are involved in BRCA1 functions in modulating G(1)/S transition, centrosome duplication, and repressing tumor formation."],"journal":["Molecular and cellular biology"],"pagination":["6983-92"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC1592852"],"repository":["biostudies-literature"],"pubmed_title":["Hyperplasia and spontaneous tumor development in the gynecologic system in mice lacking the BRCA1-Delta11 isoform."],"pmcid":["PMC1592852"],"pubmed_authors":["Cao L","Wang RH","Kim SS","Li C","Deng CX","Lim SC","Xu X","Bachelier R"],"additional_accession":[]},"is_claimable":false,"name":"Hyperplasia and spontaneous tumor development in the gynecologic system in mice lacking the BRCA1-Delta11 isoform.","description":"Alternative splicing in the BRCA1 locus generates multiple protein products including BRCA1-Delta11, which is identical to the BRCA1 full-length isoform (BRCA1-FL) except for the absence of exon 11. Mutation analysis using gene targeting to create null mutations or disrupt BRCA-FL has provided much of our understanding of BRCA1 functions; however, targeted mutation of specific short forms of BRCA1 has not been reported. To understand the physiologic functions of BRCA1-Delta11, we used a knock-in approach that blocks alternative splicing between exons 10 and 12 to prevent the formation of this form of BRCA1. We showed that homozygous mutant mice (Brca1(FL/FL)) were born at a Mendelian ratio without obvious developmental defects. However, the majority of Brca1(FL/FL) female mice showed mammary gland abnormalities and uterine hyperplasia after one year of age with spontaneous tumor formation. Cultured Brca1(FL/FL) cells exhibited abnormal centrosome amplification and reduction of G(1) population that was accompanied by accumulation of cyclin E and cyclin A. Accumulation of cyclin E was also found in epithelial layers of dilated ducts and hyperproliferative lobular regions in the mammary glands of Brca1(FL/FL) mice. These observations provide evidence that BRCA1 splicing variants are involved in BRCA1 functions in modulating G(1)/S transition, centrosome duplication, and repressing tumor formation.","dates":{"release":"2006-01-01T00:00:00Z","publication":"2006 Sep","modification":"2025-04-22T15:48:40.402Z","creation":"2019-03-27T01:46:01Z"},"accession":"S-EPMC1592852","cross_references":{"pubmed":["16943438"],"doi":["10.1128/MCB.00796-06","10.1128/mcb.00796-06"]}}