期刊
ENDOCRINOLOGY
卷 161, 期 8, 页码 -出版社
ENDOCRINE SOC
DOI: 10.1210/endocr/bqaa054
关键词
islets; mouse models; beta cells
资金
- National Institute of Diabetes and Digestive and Kidney Diseases [1R01DK110183, 1R01DK122039]
- Department of Veterans Affairs Merit [1 I01 BX003744-01]
- National Institute of Health Vanderbilt Molecular Endocrinology Training Program [5T32 DK07563]
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 Cre(ER) inserted into the Ins1 locus were generated, with the intent of producing beta 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-Cre(ER) 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.
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