Adenosine deaminase deficient transgenic mice and methods for the use thereof
AssigneeBoard of Regents, The University of Texas System
InventorsRodney E. Kellems, Surjit K. Datta, Michael R. Blackburn
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Abstract
The present invention relates to the production of adenosine deaminase (ADA) deficient mice and the use of such mice as an animal model for dysfunctions associated with elevated adenosine levels. Also, provided by the present invention are methods of treating dysfunctions associated with elevated adenosine levels and methods of screening compounds for pharmaceutical activity in the treatment of dysfunctions associated with elevated adenosine levels.
Claims15
A transgenic mouse that is homozygous for a null allele of its endogenous ADA gene, wherein:
- a) the genome of said transgenic mouse comprises a transgene comprising a mouse ADA encoding region operably coupled to a mouse placental specific ADA promoter,
- b) said ADA transgene is expressed during fetal development,
- c) there is substantially no ADA activity present in said mouse after birth, and
- d) said transgenic mouse exhibits a pulmonary abnormality after birth.
A transgenic mouse that is homozygous for a null allele of its endogenous ADA gene comprises a transgene comprising a mouse ADA encoding region operably coupled to a mouse placental specific ADA promoter, wherein ADA is present in said mouse during fetal development but substantially no endogenous ADA expression is present after birth, said mouse further characterized as exhibiting pulmonary abnormalities after birth.
A method of producing a transgenic mouse that is homozygous for a null allele of its endogenous ADA gene comprises a transgene comprising a mouse ADA encoding region operably coupled to a mouse placental specific ADA promoter, wherein ADA is present in said mouse during fetal development but substantially no endogenous ADA expression is present after birth and said mouse is further characterized as exhibiting pulmonary abnormalities, comprising:
- crossing a first mouse comprising a transgene comprising a mouse placental-specific ADA transgene with a second mouse heterozygous for null Ada allele to obtain a third mouse comprising the transgene and the null Ada allele;
- and
- crossing the third mouse with a fourth mouse to produce a fifth mouse that comprises the transgene comprising a mouse placental-specific ADA transgene and is homozygous for the null Ada allele.
Dependencies are inferred from the claim text.