A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase A develops endocrine and other tumours: comparison with Carney complex and other PRKAR1A induced lesions.

BACKGROUND: Inactivation of the human type Ialpha regulatory subunit (RIalpha) of cyclic AMP dependent protein kinase (PKA) (PRKAR1A) leads to altered kinase activity, primary pigmented nodular adrenocortical disease (PPNAD), and sporadic adrenal and other tumours. METHODS AND RESULTS: A transgenic mouse carrying an antisense transgene for Prkar1a exon 2 (X2AS) under the control of a tetracycline responsive promoter (the Tg(Prkar1a*x2as)1Stra, Tg(tTAhCMV)3Uh or tTA/X2AS line) developed thyroid follicular hyperplasia and adenomas, adrenocortical hyperplasia and other features reminiscent of PPNAD, including late onset weight gain, visceral adiposity, and non-dexamethasone suppressible hypercorticosteronaemia, with histiocytic, epithelial hyperplasias, lymphomas, and other mesenchymal tumours. These lesions were associated with allelic losses of the mouse chromosome 11 Prkar1a locus, an increase in total type II PKA activity, and higher RIIbeta protein levels; the latter biochemical and protein changes were also documented in Carney complex tumours associated with PRKAR1A inactivating mutations and chromosome 17 PRKAR1A locus changes. CONCLUSION: We conclude that the tTA/X2AS mouse line with a downregulated Prkar1a gene replicates several of the findings in Carney complex patients and their affected tissues, supporting the role of RIalpha as a candidate tumour suppressor gene.

Hadamard spectroscopy with a two-dimensional detecting array.

In a conventional grating spectrograph consisting of a single entrance slit, a grating, and a multichannel (imaging) detector, considerable light throughput advantage can be realized by replacement of the single entrance slit with a mask. This replacement can yield a signal-to-noise ratio increase because of increased light collection over an extended area of the mask when compared with a single slit. The mask produces a spectrum on the detector, which is the convolution of the mask pattern and the spectral distribution of the light source. To retrieve the spectrum, the spectrum has to be inverted. In special cases in which emission spectra are superimposed on weak backgrounds, the signal-to-noise advantage is preserved through the inversion process. Thus this technique is valuable in the observation of light sources that are produced by atomic or molecular emissions such as aurora, airglow, some interstellar emission, or laboratory spectra. Considerable signal-to-noise advantages can also be realized when the background noise of the imaging detector is not negligible. The spectral mixing of the light from the mask on the detector causes high photon fluxes on the detector, which tend to swamp the detector noise. This is a particularly important advantage in the application of CCD's as detectors because they can have significant background noise. The technique was demonstrated by computer simulations and laboratory tests.