dickkopf (dkk) genes encode a small family of secreted Wnt antagonists, except for dkk3, which is divergent and whose function is poorly understood. Here, we describe the generation and characterization of dkk3 mutant mice. dkk3-deficient mice are viable and fertile. Phenotypic analysis shows no major alterations in organ morphology, physiology, and most clinical chemistry parameters. Since Dkk3 was proposed to function as thyroid hormone binding protein, we have analyzed deiodinase activities, as well as thyroid hormone levels. Mutant mice are euthyroid, and the data do not support a relationship of dkk3 with thyroid hormone metabolism. Altered phenotypes in dkk3 mutant mice were observed in the frequency of NK cells, immunoglobulin M, hemoglobin, and hematocrit levels, as well as lung ventilation. Furthermore, dkk3-deficient mice display hyperactivity.
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http://dx.doi.org/10.1128/MCB.26.6.2317-2326.2006 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697.
Loss-of-function sequence variants in , which encodes the voltage-gated potassium channel Kv1.1, cause Episodic Ataxia Type 1 (EA1) and epilepsy. Due to a paucity of drugs that directly rescue mutant Kv1.
View Article and Find Full Text PDFACS Infect Dis
January 2025
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523, United States.
Developing new classes of drugs that are active against infections caused by is a priority for treating and managing this deadly disease. Here, we describe screening a small library of 20 DNA gyrase inhibitors and identifying new lead compounds. Three structurally diverse analogues were identified with minimal inhibitory concentrations of 0.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Selective poly(ADP-ribose) polymerase 1 (PARP1) inhibitors not only exhibit antitumor efficacy but also offer the potential to mitigate the toxicities typically associated with broader PARP inhibition. In this study, we designed and synthesized a series of small molecules targeting highly selective PARP1 inhibitors. Among these, demonstrated excellent selectivity to PARP1 along with the capability to effectively cross the blood-brain barrier (BBB).
View Article and Find Full Text PDFCalcif Tissue Int
January 2025
Musculoskeletal Disease Center (151), Jerry L. Pettis Memorial VA Medical Center, VA Loma Linda Healthcare System, 11201 Benton Street, Loma Linda, CA, 92357, USA.
This study assessed the novel concept that osteoclast-derived Grem1 has regulatory functions in the skeletal response to calcium stress using an osteoclastic Grem1 conditional knockout (cKO) mouse model. The calcium stress was initiated by feeding cKO mutants and wildtype (WT) littermates a calcium-deficient diet for 2 weeks. Deletion of Grem1 in mature osteoclasts did not affect developmental bone growth nor basal bone turnover.
View Article and Find Full Text PDFCommun Biol
January 2025
Obsidian Therapeutics, Cambridge, MA, USA.
Adoptive cell therapies (ACT) have shown reduced efficacy against solid tumor malignancies compared to hematologic malignancies, partly due to the immunosuppressive nature of the tumor microenvironment (TME). ACT efficacy may be enhanced with pleiotropic cytokines that remodel the TME; however, their expression needs to be tightly controlled to avoid systemic toxicities. Here we show T cells can be armored with membrane-bound cytokines with surface expression regulated using drug-responsive domains (DRDs) developed from the 260-amino acid protein human carbonic anhydrase 2 (CA2).
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