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Generation of a floxed Gnsa gene for the G-protein Gs alpha (G_salpha) for the construction of conditional knockout mice. The heterotrimeric G protein G_salpha couples many receptors to adenylyl cyclase and is essential for hormone-stimulated cAMP generation. Previous mouse models with germ-line mutations in Gnas, the gene that encodes G_salpha had limited usefulness in trying to decipher the role of G_salpha pathways in specific tissues since only heterozygotes were viable and could be analyzed.

Stat 5a Knockout: Stat5a deficiency results in the loss of prolactin-dependent mammary gland development and lactogenesis.

Sirt3 knockout: Sirt3 is a mitochondrial-localized tumor suppressor that maintains mitochondrial integrity and metabolism during stress.

Generation of floxed Sirtuin 6 for the construction of conditional knockout mice.

The Sirtuins (Sirt1-7), a family of seven proteins related to yeast Sir2, are histone deacetylases that regulate many critical biological processes including genomic stability, adaptation to calorie restriction and aging. Mice with a targeted disruption of Sirt6 had very low levels of blood glucose (and paradoxically, low insulin levels) and died shortly after weaning. Hypoglycemia, attributed to increased sensitivity to insulin, was the major cause for lethality.

Sirt1 knockout: Sirt1, a protein deacetylase, is a tumor suppressor that promotes genome stability and regulates proteins involved in energy metabolism.

Generation of floxed Sirtuin 1 Exon5-Exon6 for the construction of conditional knockout mice.

FGFR2 knockout is an embryonic lethal mutation and blocks limb bud initiation.

FGFR3 knockout. Complete knockout of the FGFR3 gene, the gene in which missense mutants cause short statue achondroplasia, fails to restrain cartilage growth at the bone growth plate, allowing bones to elongate excessively but fail to ossify.

The invention is an automated core biopsy instrument that may be operated with one hand. The instrument has a single activation element that causes a stylet to advance into the tissue of interest as a cutting cannula disposed around the stylet is fired to shear off the tissue into specimen notches disposed in the stylet. The invention is constructed so that the stylet and cutting cannula may be separately driven and biased. The cocking mechanism of the automated core biopsy instrument is used to cock both the stylet assembly and cutting cannula assemblies against separate biasing springs.

This molecular probe may serve as a companion tool to identify and stratify patient populations based on the prevalence of the target A₃ adenosine receptors.

Small molecule drugs, A₃AR-selective agonists, are currently in advanced clinical trials for the treatment of hepatocellular carcinoma, autoimmune inflammatory diseases, such as rheumatoid arthritis, psoriasis, and dry eye disease, and other conditions.