Multicellular living organisms and unmodified parts thereof and – Nonhuman animal – Transgenic nonhuman animal
Reexamination Certificate
2006-05-16
2006-05-16
Crouch, Deborah (Department: 1632)
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
Transgenic nonhuman animal
C800S003000, C800S021000
Reexamination Certificate
active
07045678
ABSTRACT:
A transgenic, non-human mammal useful for assessing the effect of candidate chemotherapeutic drugs on the growth of brain tumors in vivo is provided. Incorporated into the genome of the transgenic mammal, which preferably is a rodent, is a transgene which comprises a promoter comprising the nuclear factor binding region of the RR2 cis acting element of a fibroblast growth factor 1B (FGF1B) promoter. Operably linked to the promoter is reporter gene comprising a sequence which encodes the SV40 large T antigen. A transgenic, non-human mammal useful for identifying and isolating FGF1 producing brain cells. Incorporated into the genome of these transgenic animals is a transgene which comprises a promoter comprising the nuclear factor binding region of the RR2 cis acting element of an fibroblast growth factor 1B (FGF1B) promoter. Operably linked to the promoter is reporter gene comprising a sequence which encodes a protein or polypeptide other than an SV40 large T antigen. A method of obtaining neural stem cells from a sample of cells obtained from an animal is also provided. Such method comprises introducing the FGF1B-detector transgene into a sample of cells that have been obtained from the animal, and assaying for expression of the detectable marker in the cells, wherein cells that express the marker are neural stem cells. The cells which express the detectable marker can then be isolated from the population to provide a sub-population of neural stem cells.
REFERENCES:
Cameron et al. (1997) Recent Advances in Transgenic Technology. Molecular Biotechnology. 7:253-265.
Wall et al. (1996) Transgenic Livestock: Progress and Prospect for the Future. Theriogenology. 45:57-68.
Houdebine (1994) Production of Pharmaceutical proteins from transgenic animals. Journal of Biotechnology 34:269-287.
Padridge et al. (2005) The Blood-Brain Barrier:Bottleneck in Brain Drug Development. Neurox 2:3-14.
“Multiple Controlling Mechanisms of FGF1 Gene Expression through Multiple Tissue-Specific Promoters” by Chiu, et al.,Progress for Nucleic Acid Research and Molecular Biology, vol. 70, Oct., 2001, pp., 155-174.
“Neural stem cells isolated from adult FIB-Tag transgenic mice, which contain the FGF1B promoter and SV40 T antigen” by Chiu, et al., Keystone Symposia on Stem Cells: Origins, Fates and Functions, Mar. 17-23, 2002.
“Gene structure and differential expression of acidic fibroblast growth factor mRNA: identification and distribution of four different transcripts” by Myers, et al.,Oncogene, (1993) 8, 341-349.
“Functional Characterization of the Brain-specific FGF-1 Promoter, FGF-1.B” by Myers, et al.,The Journal of Biological Chemistry, vol. 270, No. 14, pp. 8257-8266, Apr. 7, 1995.
“Characterization of the 1B Promoter of Fibroblast Growth Factor 1 and Its Expression in the Adult and Developing Mouse Brain” by Alam, et al.,The Journal of Biological Chemistry, vol. 271, No. 47, pp. 30263-30271, Nov. 22, 1996.
“Transcriptional Activation of Fibroblast Growth Factor 1.B Promoter is Mediated through and 18-Base Pair cis-Acting Element” by Ray, et al.,The Journal of Biological Chemistry, vol. 272, No. 11, pp. 7546-7555, Mar. 14, 1997.
“A Splice Variant of E2-2 Basic Helix-Loop-Helix Protein Represses the Brain-specific Fibroblast Growth Factor 1 Promoter through the Binding to and Imperfect E-Box” by Liu, et al.,The Journal of Biological Chemistry, vol. 273, No. 30, pp. 19269-19276, Jul. 24, 1998.
“Characterization of the Entire Transcription Unit of the Mouse Fibroblast Growth Factor 1 (FGF-1) Gene” by Madiai, et al.,The Journal of Biological Chemistry, vol. 0274, No. 17, pp. 11937-11944, Apr. 23, 1999.
“Tumorigenesis is transgenic mice in which the SV40 T antigen is driven by the brain-specific FGF1 promoter” by Chiu, et al.,Oncogene, (2000) 19, 6229-6239.
“Plurpotency of adult neural stem cells isolated from F1B-Tag mice, which contain the FGF1 promoter and SV40 T antigen” by Chiu, et al., U.S.—Taiwan Neuroscience Symposium, Nov. 10, 2001.
“Isotopic Assays for Reporter Gene Activity” by Ausubel, et al.,Short Protocols in Molecular Biology, 3rd Edition, 1992, p. 9-28-9-30, John Wiley and Sons.
“The promoter of the human cystic fibrosis transmembrane conductance regulator gene directing SV40 T antigen expression induces malignant proliferation of epenymal cells in transgenic mice” by Perraud, et al.,Oncogene(1992) 7, 993-997.
“Establishment of SV40-tsA58 Transgenic Rats as a Source of Conditionally Immortalized Cell Lines” by Takahashi, et al.,Exp. Anim.48(4), 255-261, 1999.
Calfee Halter & Griswold LLP
Crouch Deborah
Lieto Louis D
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