Sirt6 LoxP (Sirt6tm1.1Cxd) Mouse Model for Liver Studies

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.

Hspa2 Knockout Mice for Study of Spermatogenesis and Male Infertility

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.

Human DNA Polymerase Gamma for Testing the Effect of Drugs on Mitochondrial Function

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.

Transgenic Hspa2-Cre Mice for Studying Spermatogenesis and Male Infertility

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 3(GLIS3) Knock Out (KO) Mice as Models to Screen Therapeutics for Diabetes, Polycystic Kidney Disease, and Hypothyroidism

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.