RGD Reference Report - Severe-combined immunodeficient rats can be used to generate a model of perinatal hypoxic-ischemic brain injury to facilitate studies of engrafted human neural stem cells. - Rat Genome Database

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Severe-combined immunodeficient rats can be used to generate a model of perinatal hypoxic-ischemic brain injury to facilitate studies of engrafted human neural stem cells.

Authors: Beldick, Stephanie R  Hong, James  Altamentova, Svetlana  Khazaei, Mohamad  Hundal, Anisha  Zavvarian, Mohammad-Masoud  Rumajogee, Prakasham  Chio, Jonathon  Fehlings, Michael G 
Citation: Beldick SR, etal., PLoS One. 2018 Nov 28;13(11):e0208105. doi: 10.1371/journal.pone.0208105. eCollection 2018.
RGD ID: 39938998
Pubmed: (View Article at PubMed) PMID:30485360
DOI: Full-text: DOI:10.1371/journal.pone.0208105

Cerebral palsy (CP) encompasses a group of non-progressive brain disorders that are often acquired through perinatal hypoxic-ischemic (HI) brain injury. Injury leads to a cascade of cell death events, resulting in lifetime motor and cognitive deficits. There are currently no treatments that can repair the resulting brain damage and improve functional outcomes. To date, preclinical research using neural precursor cell (NPC) transplantation as a therapy for HI brain injury has shown promise. To translate this treatment to the clinic, it is essential that human-derived NPCs also be tested in animal models, however, a major limitation is the high risk of xenograft rejection. A solution is to transplant the cells into immune-deficient rodents, but there are currently no models of HI brain injury established in such a cohort of animals. Here, we demonstrate that a model of HI brain injury can be generated in immune-deficient Prkdc knockout (KO) rats. Long-term deficits in sensorimotor function were similar between KO and wildtype (WT) rats. Interestingly, some aspects of the injury were more severe in KO rats. Additionally, human induced pluripotent stem cell derived (hiPSC)-NPCs had higher survival at 10 weeks post-transplant in KO rats when compared to their WT counterparts. This work establishes a reliable model of neonatal HI brain injury in Prkdc KO rats that will allow for future transplantation, survival, and long-term evaluation of the safety and efficacy of hiPSC-NPCs for neonatal brain damage. This model will enable critical preclinical translational research using human NPCs.



Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Prkdc  (protein kinase, DNA-activated, catalytic subunit)
Prkdcem1Sage  (protein kinase, DNA-activated, catalytic subunit; ZFN induced mutant 1, Sage)

Genes (Mus musculus)
Prkdc  (protein kinase, DNA activated, catalytic polypeptide)

Genes (Homo sapiens)
PRKDC  (protein kinase, DNA-activated, catalytic subunit)

Strains
SD-Prkdcem1Sage  (NA)


Additional Information