Transgenic pig model of cystic fibrosis
The present invention provides transgenic, large non-human animal models of diseases and conditions, as well as methods of making and using such animal models in the identification and characterization of therapies for the diseases and conditions.
1. A transgenic pig whose genome comprises a homozygous deletion of the codon for phenylalanine at position 508 of the CFTR protein of said pig, wherein said pig has a symptom of cystic fibrosis in its pancreas, intestine, liver, or gall bladder, and does not express wild-type CFTR.
2. An isolated cell of the transgenic pig of claim 1 .
3. A method of identifying a therapeutic agent that can be used in the treatment of cystic fibrosis, the method comprising administering a compound to the pig of claim 1 , wherein the pig has a symptom of cystic fibrosis in its pancreas, intestine, liver, or gall bladder, and monitoring the pig for said symptom of cystic fibrosis, wherein detection of improvement in said symptom of cystic fibrosis indicates that the compound can be used as a therapeutic agent in the treatment of cystic fibrosis.
4. The method of claim 3 , wherein the symptom of cystic fibrosis is monitored in the pancreas, intestine, or liver of the pig.
5. The transgenic pig of claim 1 , wherein the pig has a symptom of cystic fibrosis in its pancreas.
6. The transgenic pig of claim 1 , wherein the pig has a symptom of cystic fibrosis in its intestine.
7. The transgenic pig of claim 1 , wherein the pig has a symptom of cystic fibrosis in its liver.
8. The transgenic pig of claim 1 , wherein the pig has a symptom of cystic fibrosis in its gallbladder.
9. A method of making the transgenic pig of claim 1 comprising:
i) introducing a deletion into the codon for phenylalanine at position 508 of pig CFTR into a fetal pig fibroblast;
ii) introducing the nucleus of the fetal pig fibroblast into an enucleated pig oocyte to generate a pig embryo;
iii) transferring the pig embryo into a recipient female such that a transgenic pig whose genome comprises said deletion is obtained; and
iv) breeding the pig obtained in iii) such that the transgenic pig of claim 1 is obtained.
10. A transgenic pig whose genome comprises a heterozygous deletion of the codon for phenylalanine at position 508 of the CFTR protein of said pig, wherein said pig, when crossed with another transgenic pig whose genome has a heterozygous deletion of the codon for phenylalanine at position 508 of the CFTR protein of the pig, generates the transgenic pig of claim 1 .