Hair cycle and wound healing in mice with a keratinocyte-restricted deletion of FAK.

Focal adhesion kinase (FAK) is a critical component in transducing signals downstream of both integrins and growth factor receptors. To determine how the loss of FAK affects the epidermis in vivo, we have generated a mouse model with a keratinocyte-restricted deletion of fak (FAKK5 KO mice). FAK(K5 KO) mice displayed three major phenotypes--irregularities of hair cycle, sebaceous glands hypoplasia, and a thinner epidermis--pointing to defects in the proliferative capacity of multipotent stem cells found in the bulge. FAK-null keratinocytes in conventional primary culture undergo massive apoptosis hindering further analyses, whereas the defects observed in vivo do not shorten the mouse lifespan. These results suggest that the structure and the signaling environment of the native tissue may overcome the lack of signaling through FAK. Our findings point to the importance of in vivo and three-dimensional in vitro models in analyses of cell migration, proliferation, and survival. Surprisingly, the difference between FAKloxP/+ and FAKK5 KO mice in wound closure was not statistically significant, suggesting that in vivo loss of FAK does not affect migration/proliferation of basal keratinocytes in the same way as it affects multipotent stem cells of the skin.

Comparison of representative ranges based on U.S. patient population and literature reference intervals for urinary trace elements.

Reference intervals for trace elements are very hard to obtain because of the difficulty of defining a nonexposed reference population. However, representative ranges for trace elements obtained from a general patient population can provide useful information in interpreting laboratory results. We have used urine specimens submitted for trace metal analysis from patients residing in the United States to calculate representative ranges for 25 urinary trace elements, and to compare them to reference values taken from the literature. All urine analytes were measured by inductively-coupled plasma-mass spectrometry except chromium, which was measured by graphite furnace atomic absorption spectroscopy. For representative range calculation two approaches were used. In the non-parametric calculation first, the top 10% of results were discarded assuming that those specimens came from individuals with unusually high trace element exposures. Next the central 95% of the remaining data was taken as the reference interval. In the parametric calculation the specimens from exposed or not healthy individuals were assumed to appear as outliers and were discarded. The mean and S.D. were calculated, and used to determine representative ranges. The two approaches yielded very similar results, and worked remarkably well for 14 analytes. There were minor discrepancies for 7 analytes, and major for 4 analytes. All analyses of urinary trace elements included a urine creatinine value, which was used to express urinary trace element concentrations in terms of creatinine ratio. This corrects for differences in urine concentration that affects the results for random specimens.