Annotated expression and activity data for murine recombinase alleles and transgenes: the CrePortal resource

Abstract

Recombinase alleles and transgenes can be used to facilitate spatio-temporal specificity of gene disruption or transgene expression. However, the versatility of this in vivo recombination system relies on having detailed and accurate characterization of recombinase expression and activity to enable selection of the appropriate allele or transgene. The CrePortal (http://www.informatics.jax.org/home/recombinase) leverages the informatics infrastructure of Mouse Genome Informatics to integrate data from the scientific literature, direct data submissions from the scientific community at-large, and from major projects developing new recombinase lines and characterizing recombinase expression and specificity patterns. Searching the CrePortal by recombinase activity or specific recombinase gene driver provides users with a recombinase alleles and transgenes activity tissue summary and matrix comparison of gene expression and recombinase activity with links to generation details, a recombinase activity grid, and associated phenotype annotations. Future improvements will add cell type-based activity annotations. The CrePortal provides a comprehensive presentation of recombinase allele and transgene data to assist researchers in selection of the recombinase allele or transgene based on where and when recombination is desired.

The widely usedUcp1-CreEvdrtransgene elicits complex developmental and metabolic phenotypes

“…These findings highlight the importance of carefully considering the validation of transgenic lines before embarking on experimental studies. BAC Cre-drivers are usually validated only by examining spatiotemporal recombination, fueling comprehensive databases that guide selection among a large and growing number of Cre-recombinases available 4,5 . Causes for unexpected transgene expression include insertion effects on local regulation or integration of sequences leading to ectopic expression.…”

“…Validation of Cre-drivers is usually restricted to verification of specific expression in the targeted cell type. Initiatives like the CrePortal 4,5 have been invaluable for collating Cre expression data and provide a valuable resource to guide appropriate use of Cre-drivers. Yet other limitations associated with BAC transgenesis are rarely examined: (1) The insertion site of transgenes are mostly unknown; only 5.03% and 3.40% of all transgenic and Cre alleles, respectively, have mapped integration sites collated in Mouse Genome Informatics [Figure S1A-B]; (2) insertion can result in large genomic abnormalities that are not routinely inspected 6,7,8 and additionally the insertion may directly influence the phenotypes observed by different mechanisms [9][10][11][12] ; (3) passenger sequences are virtually never reported but may lead to unintended phenotypes 13 ; (4) Cre transgenes are largely used in hemizygosity masking phenotypes that would otherwise be evident 14,15 ; (5) the common absence of Cre-only control groups precludes assessment of perturbations directly attributable to the presence of the Cre transgene or protein itself.…”

Mouse Genome Informatics: an integrated knowledgebase system for the laboratory mouse

“…MGI is a founding member of the Alliance of Genome Resources (the Alliance), a confederated union of model organism databases (MODs) ( Alliance of Genome Resources Consortium 2022 ) ( https://www.alliancegenome.org/ ) and the Gene Ontology (GO) Consortium ( Ashburner et al 2000 ; Gene Ontology Consortium et al 2023 ) ( https://geneontology.org ). Other resources hosted by and integrated with MGI are the Mouse Models of Human Cancer database (MMHCdb) ( Krupke et al 2008 ), the International Mouse Strain Resource (IMSR) ( Eppig et al 2015 ), and the Recombinase (cre) Data Portal ( Perry et al 2022 ) ( https://www.informatics.jax.org/home/recombinase ). Together with these affiliated resources, MGI aims to advance our understanding of human health and disease using the mouse as a model system.…”

Refined Tamoxifen Administration in Mice by Encouraging Voluntary Consumption of Palatable Formulations

“…For more than 20 years, tamoxifen has been utilized in research to induce spatiotemporal modifications in gene expression in Cre-ER T1/T2 /loxP transgenic mouse models [11][12][13][14] . The number of CreER T1 and CreER T2 mouse models generated for research exceeded 1,000 by June 2021 15 , and an additional 100 models were generated in the last year alone (as of May 2022) [15][16][17] . Despite its routine use in research, there is no consensus on the best method for TAM delivery 11 .…”