Biomedical subjects

Andreas F Kolb

Publications and source records attributed to Andreas F Kolb.

3 recordsLinked to original sources

PubMed2002

Structure and regulation of the murine gamma-casein gene.

The murine casein locus consists of five genes, which are coordinately regulated during mammary development. The levels of casein-specific mRNAs in mammary epithelial cells increase during the second half of pregnancy and remain high during lactation. The murine gamma-casein gene, which corresponds to the alphaS2-casein gene in ruminants, was isolated from a mouse bacterial artificial chromosome (BAC) library (strain 129SV). The gene contains 14 exons, which are distributed over 14 kb of DNA sequence. The expression pattern of the murine gamma-casein gene mimics that of the neighbouring beta-casein gene in terms of developmental induction in vivo. In cell culture, both the beta- and gamma-casein promoter are synergistically induced by prolactin and glucocorticoids. Glucocorticoid induction is critically dependent on prolactin-mediated activation of STAT5 in both promoters. Several consensus STAT5 binding sites were identified in the gamma-casein promoter, some of which may have an additive effect on prolactin induction. mRNA levels of gamma- and beta-casein are similar in lactating mammary tissue. However, promoter segments derived from the gamma-casein gene are significantly less active in cell culture than comparable fragments of the beta-casein promoter. Promoter hybrids between the gamma- and beta-casein promoters revealed that the critical sequences which are responsible for the different in vitro activity are located in a short promoter proximal region.

Animals↗

PubMed2002

Engineering immunity in the mammary gland.

The major physiological function of milk is the transport of amino acids, carbohydrates, lipids, and minerals to mammalian offspring. However, milk is also a rich collection of antimicrobial substances, which provide protection against pathogenic infections. These molecules safeguard the integrity of the lactating mammary gland, but also provide protection for the suckling offspring during a time when its immune system is still immature. The protective substances can be classified into two categories: 1) nonspecific defense substances, which provide innate immunity, and 2) molecules such as antibodies, which provide adaptive immunity and are directed against specific pathogens. The antimicrobial potency of milk has not been a target for farm animal breeding in the past, and present day ruminants provide suboptimal levels of antimicrobial substances in milk. Altered breeding regimes, pharmacological intervention, and transgenesis can be utilized to improve the antimicrobial properties of milk. Such alterations of milk composition have implications for human and animal health.

Animals↗

PubMed2002

Genome engineering using site-specific recombinases.

The targeted modification of the mammalian genome has a variety of applications in research, medicine, and biotechnology. Site-specific recombinases have become significant tools in all of these areas. Conditional gene targeting using site-specific recombinases has enabled the functional analysis of genes, which cannot be inactivated in the germline. The site-specific integration of adeno-associated virus, a major gene therapy vehicle, relies on the recombinase activity of the viral rep proteins. Site-specific recombinases also allow the precise integration of open reading frames encoding pharmaceutically relevant proteins into highly active gene loci in cell lines and transgenic animals. These goals have been accomplished by using a variety of genetic strategies but only a few recombinase proteins. However, the vast repertoire of recombinases, which has recently become available as a result of large-scale sequencing projects, may provide a rich source for the development of novel strategies to precisely alter mammalian genomes.

Animals↗