PTEN-induced kinase 1 (PINK1), which is associated with early onset Parkinson disease, encodes a serine-threonine kinase that is critical for maintaining mitochondrial function. Moreover, another Parkinson disease-linked gene, parkin, functions downstream of PINK1 in protecting mitochondria and dopaminergic (DA) neuron. In our fly genetic screening, knockdown of Sir2 blocked PINK1 overexpressio...

We report a direct comparison of the differential effects of individual p53 mutations on lung tumor growth and progression, and the creation of a murine model of spontaneous advanced lung adenocarcinoma that closely recapitulates several aspects of advanced human pulmonary adenocarcinoma. We generated compound conditional knock-in mice with mutations in K-ras combined with one of three p53 alle...

Hox genes are crucial for body axis specification during embryonic development. Hoxa11 plays a role in anteroposterior patterning of the axial skeleton, development of the urogenital tract of both sexes, and proximodistal patterning of the limbs. Hoxa11 expression is also observed in the neural tube. Herein, we report the generation of a Hoxa11eGFP targeted knock-in allele in mice in which eGFP...

Human heart development requires an orderly coordination of transcriptional programs, with the homeodomain protein NKX2-5 being one of the key transcription factors required for the differentiation of mesodermal progenitor cells. Indeed, lack of Nkx2-5 in mice arrests heart development prior to looping, resulting in embryonic lethality. There are 28 germline NKX2-5 mutations identified in human...

Planar cell polarity (PCP) refers to the collective polarization of cells along a tissue plane, such as ordered alignment body hairs in skin. Disruption PCP leads developmental disorders heart, neural tube, inner ear and A hallmark feature is asymmetric localization core proteins Fz6 Vangl2 at an intercellular junctional complex organized by cadherin family member Celsr1. Our studies Celsr1 mou...

Rare missense mutations in the von Willebrand factor (VWF) A3 domain that disrupt collagen binding, have been found in patients with a mild bleeding phenotype. However, the analysis of these aberrant VWF-collagen interactions has been limited. Here, we have developed mouse models of collagen binding mutants and analyzed the function of the A3 domain using comprehensive in vitro and in vivo appr...

Defects in pancreatic -cell function contribute to the development of type 2 diabetes, a polygenic disease that is characterized by insulin resistance and compromised insulin secretion. Hepatocyte nuclear factors (HNFs) -1 , -3 , -4 , and Pdx-1 contribute in the complex transcriptional circuits within the pancreas that are involved in -cell development and function. In mice, a heterozygous muta...

aim : to induce acute colitis progresses to chronicity in c57bl/6 mice by dextran sulfate sodium.   background : murine models are essential tools to understand ibd pathogenesis. among different types of chemically induced colitis models, the dextran sulfate sodium (dss)-induced colitis model is the most common model of ibd, due to its simplicity. patients and methods : male c57bl/6 mice 6–8 we...

We present a detailed study of the genetic basis of mesodermal axial patterning by paralogous group 8 Hox genes in the mouse. The phenotype of Hoxd8 loss-of-function mutants is presented, and compared with that of Hoxb8- and Hoxc8-null mice. Our analysis of single mutants reveals common features for the Hoxc8 and Hoxd8 genes in patterning lower thoracic and lumbar vertebrae. In the Hoxb8 mutant...