development of a canine model of scid
TRANSCRIPT
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Slide 5
Development of a canine model of SCID
Basis of immunodeficiency:
defective VDJ recombination
MSUTom BellLisa AllenCheri JohnsonBryden
StanleyAri JutkowitzTom Mullaney
Mark Bell Sarah MarshMichele Fritz
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Like C.B17 SCID mice, SCID dogs have a null mutation in DNA-PKcs
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Why develop a canine model of SCID?-as models of NHEJ deficiency genomic instability cancer predisposition embryonic neuronal apoptosis
-as models for bone marrow transplantation, to progress transplants for SCID children
-as substitutes for SCID mice? tumor models autoimmunity models
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Immune reconstituted SCID dogs have normal lymphoid tissues with a high level of donor chimerism
Immune reconstituted dogs are immunocompetent and do not require special housing, making it feasible to actually derive a colony of SCID dogs for research.
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With help of in vivo pharmacology group, and UCRFdevised protocols to maintain immunocompromised animals for extended periods.
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SCID dogs are excellent hosts for human xenografts.
tested:
human ovarian carcinoma
human fibrosarcoma
rodent skin xenografts
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What I would do with a large animal genome editing facility
Murine models of DNA repair deficits don't always recapitulate the human disease
DNA-PKcs
Ataxia telangiectasia (ATM kinase)
Fanconi anemia (17 different genes, FANC A-S)
Spinocerebellar ataxia with axonal neuropathy (SCAN) (TDP1)