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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.

HSPA2 is a member of the HSP70 family of heat-shock proteins that serve as molecular chaperones. Researchers discovered that HSPA2 protein is expressed in spermatogenesis during the meiotic phase. Spermatogenic cells lacking the HSPA2 protein arrest in mid-meiosis and undergo apoptosis. HSPA2 is present in the synaptonemal complex of wild-type mice and the chromosomes fail to separate in HSPA2-deficient mice (previously known as Hsp70-2-/- mice), suggesting that HSPA2 is required for the chromosomal events of meiosis such as synapsis, crossing over, or recombination.

One of the primary means for treating HIV infection is the use of antiviral nucleotide or nucleoside analogs. These analogs work by inhibiting the activity of reverse transcriptase, the enzyme responsible for preparing the HIV genome for integration into the DNA of the host cell. Although these analogs do not have an effect on the polymerases responsible for replicating the human genome, the polymerase responsible for replicating the mitochondrial genome is sensitive to these analogs.

HSPA2 is a member of the HSP70 family of heat-shock proteins that serve as molecular chaperones. Hspa2-cre expression mimics the spermatogenic cell-specific expression of endogenous HSPA2 within the testis, being first observed in leptotene/zygotene spermatocytes. Expression of the transgene is also detected at restricted sites in the brain, as occurs for endogenous HSPA2.

GLI-similar (Glis) 1-3 proteins constitute a subfamily of the Krüppel-like zinc finger transcription factors that are closely related to the Gli family. Mutations in human GLIS3 have been implicated in a syndrome characterized by neonatal diabetes and congenital hypothyroidism (NDH) and in some patients accompanied by polycystic kidney disease, glaucoma, and liver fibrosis. To further identify and study the physiological functions of GLIS3, NIEHS investigators generated mice in which GLIS3 is ubiquitously knocked out (GLIS3-KO) or conditionally knocked out in a cell type-specific manner.

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.