The NLRP3 inflammasome is essential for caspase-1 activation and the release of interleukin (IL)-1ß, IL-18, and gasdermin-D in myeloid cells. However, research on species-specific NLRP3’s physiological impact is limited. We engineer mice with the human NLRP3 gene, driven by either the human or mouse promoter, via syntenic replacement at the mouse Nlrp3 locus. Both promoters facilitate hNLRP3 expression in myeloid cells, but the mouse promoter responds more robustly to LPS. Investigating the disease impact of differential NLRP3 regulation, we introduce the D305N gain-of-function mutation into both humanized lines. Chronic inflammation is evident with both promoters; however, CNS outcomes vary significantly. Despite poor response to LPS, the human promoter results in D305N-associated aseptic meningitis, mirroring human pathology. The mouse promoter, although leading to increased CNS expression post-LPS, does not induce meningitis in D305N mutants. Therefore, human-like NLRP3 expression may be crucial for accurate modeling of its role in disease pathogenesis.

These mice have no functional factor IX protein, which is an intrinsic clotting factor deficient in human victims of hemophilia B. They may be used in preclinical trials to screen possible human hemophilia B drugs. If you are an academic institution or nonprofit organization interested in this research tool for noncommercial purposes, please contact the researcher directly to inquire about availability.

Model designed as a positive readout test for activity, delivery, and distribution of antisense oligomers. The expressed gene (EGFP-654) encoding enhanced green fluorescence protein is interrupted by an aberrantly spliced mutated intron of the human beta-globin gene. Aberrant splicing of this intron prevented expression of EGFP-654 in all tissues, whereas in tissues and organs that took up a splice site-targeted antisense oligomer, correct splicing was restored and EGFP-654 expression upregulated. This research tool is only available from The Jackson Laboratory at https://www.jax.org/strain/027617.

This mouse line expresses the reporter gene EGFP from the promoter of FoxJ1: a transcription factor whose expression is restricted to cells possessing motile cilia or flagella. This promoter has been demonstrated to be highly specific for motile ciliated cells, and transgene-positive mice demonstrate strong EGFP expression in the ciliated cells of tracheal, bronchial, and nasal epithelium. These mice were developed in order to identify a desirable, cell-specific promoter to use in gene therapy for cystic fibrosis as described in the listed publication. In addition to cystic fibrosis, these mice could potentially be used in studies of other diseases that affect ciliated cells such as chronic respiratory infections and polycystic kidney disease. These mice are available at The Jackson Laboratory and can be found at https://www.jax.org/strain/010827.  

In neurons, activation of hM4Di induces neuronal silencing. This model can be used to selectively and reversibly suppress hippocampal neuronal activity during synaptic consolidation. Clozapine-N-oxide induces Gi activation and allows in vivo manipulation of neuronal activity in freely moving animals. This mouse line is available from The Jackson Laboratory and can be found at https://www.jax.org/strain/026219. 

Adora2A-rM3Ds transgenic mice express a fluorescent protein reporter and a mutant G protein-coupled receptor, rM3Ds, directed to D2-dopamine receptor-expressing striatopallidal medium spiny neurons by the Adora2a promoter/enhancer regions of a BAC transgene. The rM3Ds receptor can be activated by clozapine-N-oxide allowing selective and non-invasive modulation of Gαs– signaling in specific neuronal populations in vivo. If you are an academic institution or nonprofit organization interested in this research tool for noncommercial purposes, please contact the researcher directly to inquire about availability.

Certain G protein-coupled receptors related to asthma (GPRA) polymorphisms have been linked to asthma.  Furthermore, GPRA has been shown to reduce cell growth in HEK-293H cells. GPRA modulators intended to treat asthma or alter cell growth can be screened with these mice. UNC has developed both mouse GPRA knockout mice and human GPRA knockout mice (huGPRA). If you are an academic institution or nonprofit organization interested in this research tool for noncommercial purposes, please contact the researcher directly to inquire about availability.

Transgenic mice expressing an evolved G protein-coupled receptor (hM3Dq) selectively activated by the pharmacologically inert, orally bioavailable drug clozapine-N-oxide (CNO). Behavioral correlates of neuronal activation included increased locomotion, stereotypy, and limbic seizures. If you are an academic institution or nonprofit organization interested in this research tool for noncommercial purposes, please contact the researcher directly to inquire about availability.

Angiotensin converting enzyme 2 (ACE2) is the cellular entry receptor for many SARS-like coronaviruses. SARS-CoV and SARS-CoV-2 bind and enter human cells via the ACE2 receptor.  This mouse line expresses human ACE2 under the control of HFH4, a lung ciliated epithelial promoter. HFH4-hACE2-expressing mice are sensitized to infection by SARS-like coronaviruses when compared with wild-type mice. Wild-type mice do not develop clinical disease, however, this mouse strain was developed to express human ACE2 which allows for testing in mice that develop clinical disease upon infection. When infected with SARS-CoV Urbani, HFH4-hACE2-expressing mice experienced no weight loss for the first 3 days, but then experienced rapid weight loss and death between days 4 and 5. This mouse line shows value as a model to study coronavirus pathogenesis and to test therapeutic and vaccine efficacy against such coronaviruses.     This research tool is available from the Mutant Mouse Resource and Research Center (MMRRC) at the following link: https://www.mmrrc.org/catalog/sds.php?mmrrc_id=66719.

Mice expressing human type I (IL-4)  and type II (IL-4 and IL-13) receptors. If you are an academic institution or nonprofit organization interested in this research tool for noncommercial purposes, please contact the researcher directly to inquire about availability.