A splice donor mutation in NAA10 results in the dysregulation of the retinoic acid signalling pathway and causes Lenz microphthalmia syndrome.

Introduction: Lenz microphthalmia syndrome (LMS) is a genetically heterogeneous X-linked disorder characterised by microphthalmia/anophthalmia, skeletal abnormalities, genitourinary malformations, and anomalies of the digits, ears, and teeth. Intellectual disability and seizure disorders are seen in about 60% of affected males. To date, no gene has been identified for LMS in the microphthalmia syndrome 1 locus (MCOPS1).

Prepubertal OVX increases IGF-I expression and bone accretion in C57BL/6J mice.

It is generally well accepted that the pubertal surge in estrogen is responsible for the rapid bone accretion that occurs during puberty and that this effect is mediated by an estrogen-induced increase in growth hormone (GH)/insulin-like growth factor (IGF) action. To test the cause and effect relationship between estrogen and GH/IGF, we evaluated the consequence of ovariectomy (OVX) in prepubertal mice (C57BL/6J mice at 3 wk of age) on skeletal changes and the GH/IGF axis during puberty. Contrary to our expectations, OVX increased body weight (12-18%), bone mineral content (11%), bone length (4%), bone size (3%), and serum, liver, and bone IGF-I (30-50%) and decreased total body fat (18%) at 3 wk postsurgery.

Tumor necrosis factor-alpha augments matrix metalloproteinase-9 production in skeletal muscle cells through the activation of transforming growth factor-beta-activated kinase 1 (TAK1)-dependent signaling pathway.

We have investigated the effect of tumor necrosis factor-alpha (TNF-alpha) on the production of extracellular matrix-degrading proteases in skeletal muscles. Using microarray, quantitative PCR, Western blotting, and zymography, we found that TNF-alpha drastically increases the production of matrix metalloproteinase (MMP)-9 from C2C12 myotubes. In vivo administration of TNF-alpha in mice increased the transcript level of MMP-9 in skeletal muscle tissues.

Digit tip regrowth and differential gene expression in MRL/Mpj, DBA/2, and C57BL/6 mice.

MRL/Mpj mice are the only known strain of mouse that can regenerate cardiac lesions and completely heal ear punches without scarring. This study was undertaken to determine if MRL mice also have greater regrowth capabilities in amputated digit tips. Right paw digit tips of neonatal MRL mice were dissected, with the left front paws as uncut controls.

Whole genome microarray analysis of growth hormone-induced gene expression in bone: T-box3, a novel transcription factor, regulates osteoblast proliferation.

Growth hormone (GH) is important in the development and maintenance of bone; however, the IGF-dependent and -independent molecular pathways involved remain to be established. We used microarray analysis to evaluate GH signaling pathways in 4-wk-old GH-deficient mice following a single injection of GH (4 mg/kg body wt) or PBS (n = 6/group) at 6 or 24 h after treatment. Six thousand one hundred sixty genes were differentially expressed at P View Article and Find Full Text PDF

Microarray analysis of gene expression during the inflammation and endochondral bone formation stages of rat femur fracture repair.

Microarray analysis of gene expression was performed in the healing femur fractures of 13-week-old male rats during the inflammatory stage of repair, at 3 days post-fracture, and the endochondral bone formation stage of repair, at 11 days post-fracture. Multiple replicate pairs of fracture tissues paired with unfractured tissues, and unfractured control bones that had the stabilizing K-wire were introduced. This approach normalized the marrow contributions to the RNA repertoire.

Global gene expression analysis in the bones reveals involvement of several novel genes and pathways in mediating an anabolic response of mechanical loading in mice.

To identify the genes and signal pathways responsible for mechanical loading-induced bone formation, we evaluated differential gene expression on a global basis in the tibias of C57BL/6J (B6) mice after four days of four-point bending. We applied mechanical loads to the right tibias of the B6 mice at 9 N, 2 Hz for 36 cycles per day, with the left tibias used as unloaded controls. RNA from the tibias was harvested 24 h after last stimulation and subjected to microarray.

Spontaneous fractures in the mouse mutant sfx are caused by deletion of the gulonolactone oxidase gene, causing vitamin C deficiency.

Unlabelled: Using a mouse mutant that fractures spontaneously and dies at a very young age, we identified that a deletion of the GULO gene, which is involved in the synthesis of vitamin C, is the cause of impaired osteoblast differentiation, reduced bone formation, and development of spontaneous fractures.

Introduction: A major public health problem worldwide, osteoporosis is a disease characterized by inadequate bone mass necessary for mechanical support, resulting in bone fracture. To identify the genetic basis for osteoporotic fractures, we used a mouse model that develops spontaneous fractures (sfx) at a very early age.

EGFR and EGFRvIII expression in primary breast cancer and cell lines.

EGFRvIII is a constitutively activated truncated variant of the epidermal growth factor receptor (EGFR) which has been shown to increase tumorgenicity. There are conflicting reports on the extent of EGFRvIII expression in tissues which may in part stem from the use of different assay methodologies. We investigated the expression of both EGFRvIII and wild-type EGFR (EGFRwt) in cell lines and primary breast cancers.

Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1: high-throughput SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls.

beta-Defensins are cationic antimicrobial peptides expressed in epithelia. They exhibit antibacterial, antifungal, and antiviral properties. Defensins are a component of the innate immune response, and it has been proposed that they have a protective role in the oral cavity.

A polymorphism in the CYP17 gene and risk of prostate cancer.

Steroid hormones are important in the etiology and progression of prostate cancer, and expression of genes involved in hormone production may alter susceptibility. One such gene is CYP17, which encodes the cytochrome P450c17a enzyme responsible for the biosynthesis of testosterone. A T to C transition (A2 allele) in the 5' promoter region of the gene is hypothesized to increase the rate of gene transcription, increase androgen production, and thereby increase risk of prostate cancer.