Topical drug rescue strategy and skin protection based on the role of Mc1r in UV-induced tanning

Ultraviolet-light (UV)-induced tanning is defective in numerous 'fair-skinned' individuals, many of whom contain functional disruption of the melanocortin 1 receptor (MC1R). Although this suggested a critical role for the MC1R ligand melanocyte stimulating hormone (MSH) in this response, a genetically controlled system has been lacking in which to determine the precise role of MSH-MC1R. Here we show that ultraviolet light potently induces expression of MSH in keratinocytes, but fails to stimulate pigmentation in the absence of functional MC1R in red/blonde-haired Mc1r(e/e) mice. However, pigmentation could be rescued by topical application of the cyclic AMP agonist forskolin, without the need for ultraviolet light, demonstrating that the pigmentation machinery is available despite the absence of functional MC1R. This chemically induced pigmentation was protective against ultraviolet-light-induced cutaneous DNA damage and tumorigenesis when tested in the cancer-prone, xeroderma-pigmentosum-complementation-group-C-deficient genetic background. These data emphasize the essential role of intercellular MSH signalling in the tanning response, and suggest a clinical strategy for topical small-molecule manipulation of pigmentation.     

The finished DNA sequence of human chromosome 12

Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents.     

Reiteration frequency of the gene for tissue-specific histone H5 in the chicken genome.

Chicken erythroid cells contain a tissue specific histone known as H5 in addition to the five major histone species found in other organisms. The mRNA coding for this histone has been isolated by indirect immunoprecipitation from immature, non-dividing reticulocytes in which this is the only histone synthesised. The mRNA has been modified by the enzymatic addition of a 3' polyadenylic acid tract, and transcribed into complementary DNA (cDNA) using the RNA-dependent DNA-polymerase from avian myeloblastosis virus. Studies on the hybridisation of this cDNA indicate that the gene coding for the H5 histone is reiterated 10 times in the chicken genome.     

Allele-specific PCR reveals thatCYP6D1 is on chromosome 1 in the house fly,Musca domestica

A cytochrome P450, termed P450lpr, is the major P450 responsible for pyrethroid resistance in the Learn-PyR (LPR) strain of house fly. Recently, the putative gene (CYP6D1) coding for P450_lpr has been sequenced from the LPR and aabys strains of house fly. Allele-specific polymerase chain reaction (ASPCR) was used for linkage group analysis with backcross progeny from the wild type LPR strain and a multiple marker strain (aabys). We found thatCYP6D1 is linked to chromosome 1. The possible role of regulatory or modifying genes responsible for elevated P450_lpr expression is discussed in relation to the chromosomal linkage ofCYP6D1.