Ernest Orlando Lawrence Berkeley National Laboratory
APPLICATIONS OF TECHNOLOGY:
- Research into factors involved in atherosclerosis
- Investigation into pharmacological agents that may affect expression of proatherogenic human proteins
- Mice express genomic human proteins
- Apolipoprotein (a)
Apo(a) plasma concentration is a major independent risk factor for atherosclerosis in humans. For the first time, researchers have a tool to study factors that determine regulation of apo(a) expression, and to investigate pharmacological agents that may affect expression of this proatherogenic human protein. These mice express a yeast artificial chromosome containing the entire apoliprotein(a) gene, including the apo(a) sequence with the appropriate normal regulatory elements. Berkeley Labs mice differ from other apo(a) cDNA constructs by the presence of all the introns and sequences of significant lengths both 5' and 3' to the apo(a) structural gene.
REFERENCE NUMBER: IB-1042, 1115
Human apoB transgenic mice will serve as a model for developing pharmacological approaches to lower the levels of apoB in humans. Researchers can use these mice to develop gene or drug therapy approaches that impact on apoB plasma concentrations, as well as study its interaction with other plasma proteins such as apo(a)
REFERENCE NUMBER: IB-1117
Using these mice, researchers can study the properties of the apoAIMilano gene product on high density lipoprotein (HDL) metabolism and atherosclerosis, and inves-ti-gate whether the apoAIMilano gene product does, indeed, have the truly beneficial effects on atherosclerosis, fibrinolysis, and restinosis properties that have been attributed to this molecule in humans but have not been critically evaluated.
REFERENCE NUMBER: 1116
Scientists at Berkeley Lab have created a strain of transgenic mice harboring several human BACs that include a large genomic fragment and regulatory elements of the human ABC-1 (ATP Binding Cassette Transporter 1) gene. The expression of the human ABC-1 gene is under the control of the human ABC1 regulatory sequences in these mice. Expression of the transgene was assessed by RT-PCR and shown to be positive in brain, liver, kidney, adrenal, and heart tissue. The relative levels of expression of the human transgene in these different tissues reflect that determined for the endogenous mouse ABC-I gene. The highest level of expression is in the liver. The background of the ABC1 transgenic mice is pure FVB, and they have been continuously maintained in this inbred background. With transgenic mice expressing human ABC-1, it may be possible to study in vivo factors affecting expression of this gene. ABC-1 is a recently discovered participant in the metabolism of HDL whose regulation may play a vital role in determining HDL levels. Currently, human cell cultures allow study only of in vitro expression of this human gene . This transgenic mouse strain will be used in pharmacological research to screen for compounds that alter expression of the ABC-1 gene.
Berkeley Lab's ABC-1 transgenic mice are available for licensing and bailment.
REFERENCE NUMBER: 1674
STATUS: Available for licensing/bailment
FOR MORE INFORMATION:
G. G. Loots, R. M. Locksley, C. M. Blankespoor, Z. E. Wang, W. Miller,4 E. M. Rubin, K. A. Frazer. "Intificatiion of a Coordinate
Regulator of Interleukins 4, 13, and 5 by Cross-Species Sequence Comparisons" Science Magazine. Vol 288, pg 136-140, 2000
REFERENCE NUMBER: See above
SEE THESE OTHER BERKELEY LAB TECHNOLOGIES IN THIS FIELD:
- Newly Identified Apolipoprotein, IB-1709