Biomedical subjects
Laura K Cole
Publications and source records attributed to Laura K Cole.
The role of Pax2 in mouse inner ear development.
The paired box transcription factor, Pax2, is important for cochlear development in the mouse inner ear. Two mutant alleles of Pax2, a knockout and a frameshift mutation (Pax21Neu), show either agenesis or severe malformation of the cochlea, respectively. In humans, mutations in the PAX2 gene cause renal coloboma syndrome that is characterized by kidney abnormalities, optic nerve colobomas and mild sensorineural deafness. To better understand the role of Pax2 in inner ear development, we examined the inner ear phenotype in the Pax2 knockout mice using paint-fill and gene expression analyses. We show that Pax2-/- ears often lack a distinct saccule, and the endolymphatic duct and common crus are invariably fused. However, a rudimentary cochlea is always present in all Pax2 knockout inner ears. Cochlear outgrowth in the mutants is arrested at an early stage due to apoptosis of cells that normally express Pax2 in the cochlear anlage. Lack of Pax2 affects tissue specification within the cochlear duct, particularly regions between the sensory tissue and the stria vascularis. Because the cochlear phenotypes observed in Pax2 mutants are more severe than those observed in mice lacking Otx1 and Otx2, we postulate that Pax2 plays a key role in regulating the differential growth within the cochlear duct and thus, its proper outgrowth and coiling.
Fish oil containing phytosterol esters alters blood lipid profiles and left ventricle generation of thromboxane a(2) in adult guinea pigs.
This study was designed to investigate the lipid-lowering ability of a novel dietary ingredient composed of phytosterols esterified to (n-3) polyunsaturated fatty acids (PUFA) [PS(n-3)]. Adult guinea pigs were fed a test diet supplemented with PS(n-3) (25 g/kg) and corn oil (CO, 5 g/kg), whereas the diet fed to control guinea pigs was supplemented with CO only (30 g/kg). Cholesterol was added to both diets (0.8 g/kg). After 3-4 wk of consuming the diets, serum total cholesterol (TC) and triacylglycerol (TAG) in the PS(n-3) group were 36 and 29% lower, respectively, than levels in controls (P < 0.05). The lower TC levels in the PS(n-3) group reflected a 38% reduction in non-HDL cholesterol (non-HDL-C), whereas the HDL-C concentration was unaffected. Analysis of cardiac left ventricle indicated that generation of the proaggregatory, arrhythmic eicosanoid, thromboxane A(2), was >60% lower in the PS(n-3)-supplemented guinea pigs than in CO controls (P < 0.001). This study demonstrates that the TAG-lowering and eicosanoid-modifying properties of the fish oil (n-3) PUFA are retained when they are provided in the diet in ester linkage with hypocholesterolemic phytosterols.