Homologous recombination for animal model exhibiting reduced lev

Details Homologous recombination for animal model exhibiting reduced lev Homologous recombination for animal model exhibiting reduced lev

1996-07-15

1999-02-09

Chambers, Jasemine C.

Multicellular living organisms and unmodified parts thereof and

Nonhuman animal

4351723, 800DIG1, C12N 500, C12N 1500

Patent

active

058697187

ABSTRACT:
Transgenic non-human mammals and methods of preparing such mammals are disclosed. Homologous recombination is employed to inactivate genes, particularly genes coding for neuronal intermediate filaments. These animals, whose phenotype is characterized by reduced or eliminated levels of a neuronal intermediate filament, are useful as models for studying aging, injury to the nervous system, and pathogenesis of neurodegenerative diseases. They are also useful for the screening of potential therapeutic agents.

REFERENCES:
McCall et al., "Targeted deletion in astrocyte intermediate filament (Gfap) alters neuronal physiology," Proc. Natl. Acad. Sci., USA, vol. 93, pp. 6361-6366, Jun. 1996.
Colucci-Guyon et al., "Mice Lacking Vimentin Develop and Reproduce without an Obvious Phenotype," Cell, vol. 79, pp. 679-694, Nov. 18, 1994.
Galou et al., "Disrupted Glial Fibrillary Acidic Protein Network in Astrocytes from Vimentin Knockout Mice", The Journal of Cell Biology, vol. 133, No. 4, May 1996, pp. 853-863.
Friedman et al, Transgenic mouse approaches for analysis of the nervous system, NeuroProtocols, vol. 3, No. 1, pp. 69-80, Aug. 1993.
Eyer et al, Neurofilament-deficient axons and perikaryal aggregates in viable transgenic mice expressing a neurofilament-beta-galactosidase fusion protein, Neuron, vol. 12, No. 2 pp. 389-405, Feb. 1994.
Plummer et al, Accelerated and widespread neuronal loss occurs in motor neuron degeneration (mnd) mice expressing a neurofilament-disrupting transgene. Mol, and Cell. NeuroSci., vol. 6, No. 6, pp. 532-543, Dec. 1995.
Mansour et al, Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature, vol. 336, pp. 349-352, Nov. 24, 1988.

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