دورية أكاديمية
أعرض في EDS

Ins1-Cre and Ins1-CreER Gene Replacement Alleles Are Susceptible To Silencing By DNA Hypermethylation.

التفاصيل البيبلوغرافية
العنوان: Ins1-Cre and Ins1-CreER Gene Replacement Alleles Are Susceptible To Silencing By DNA Hypermethylation.
المؤلفون: Mosleh E; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Ou K; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Haemmerle MW; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Tembo T; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Yuhas A; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Carboneau BA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee., Townsend SE; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee., Bosma KJ; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee., Gannon M; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee.; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.; United States Department of Veteran Affairs, Nashville, Tennessee., O'Brien RM; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee., Stoffers DA; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Golson ML; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland.
المصدر: Endocrinology [Endocrinology] 2020 Aug 01; Vol. 161 (8).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375040 Publication Model: Print Cited Medium: Internet ISSN: 1945-7170 (Electronic) Linking ISSN: 00137227 NLM ISO Abbreviation: Endocrinology Subsets: MEDLINE
أسماء مطبوعة: Publication: 2017- : New York : Oxford University Press
Original Publication: Los Angeles, Calif. : Association for the Study of Internal Secretions,
مواضيع طبية MeSH: DNA Methylation/*genetics , Insulin/*genetics , Insulin-Secreting Cells/*metabolism , Integrases/*genetics , Recombination, Genetic/*genetics, Alleles ; Animals ; Cells, Cultured ; Female ; Gene Silencing ; HEK293 Cells ; Humans ; Insulin/metabolism ; Insulin-Secreting Cells/physiology ; Integrases/metabolism ; Islets of Langerhans/metabolism ; Islets of Langerhans/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Organ Specificity/genetics
مستخلص: Targeted gene ablation studies of the endocrine pancreas have long suffered from suboptimal Cre deleter strains. In many cases, Cre lines purportedly specific for beta cells also displayed expression in other islet endocrine cells or in a subset of neurons in the brain. Several pancreas and endocrine Cre lines have experienced silencing or mosaicism over time. In addition, many Cre transgenic constructs were designed to include the hGH mini-gene, which by itself increases beta-cell replication and decreases beta-cell function. More recently, driver lines with Cre or CreER inserted into the Ins1 locus were generated, with the intent of producing β cell-specific Cre lines with faithful recapitulation of insulin expression. These lines were bred in multiple labs to several different mouse lines harboring various lox alleles. In our hands, the ability of the Ins1-Cre and Ins1-CreER lines to delete target genes varied from that originally reported, with both alleles displaying low levels of expression, increased levels of methylation compared to the wild-type allele, and ultimately inefficient or absent target deletion. Thus, caution is warranted in the interpretation of results obtained with these genetic tools, and Cre expression and activity should be monitored regularly when using these lines.
(© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
التعليقات: Comment in: Endocrinology. 2020 Aug 1;161(8):. (PMID: 32422652)
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معلومات مُعتمدة: F31 DK117577 United States DK NIDDK NIH HHS; R01 DK110183 United States DK NIDDK NIH HHS; R01 DK120626 United States DK NIDDK NIH HHS; R01 DK121175 United States DK NIDDK NIH HHS; R01 DK122039 United States DK NIDDK NIH HHS; T32 DK007563 United States DK NIDDK NIH HHS; I01 BX003744 United States BX BLRD VA; R01 DK105689 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: beta cells; islets; mouse models
المشرفين على المادة: 0 (Ins1 protein, mouse)
0 (Insulin)
EC 2.7.7.- (Cre recombinase)
EC 2.7.7.- (Integrases)
تواريخ الأحداث: Date Created: 20200409 Date Completed: 20210104 Latest Revision: 20210612
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7354059
DOI: 10.1210/endocr/bqaa054
PMID: 32267917
قاعدة البيانات: MEDLINE
الوصف
تدمد:1945-7170
DOI:10.1210/endocr/bqaa054