title: Partial IFN-alpha/beta and IFN-gamma receptor knockout trisomy 16 mouse fetuses show improved growth and cultured neuron viability.
abstract: The trisomy 16 mouse fetus is a well-studied model for Down syndrome (trisomy 21), the leading genetic cause of mental retardation in the newborn population. Human chromosome 21 and mouse chromosome 16 each carry a large cluster of genes that code for components of the interferon (IFN)-alpha/beta and IFN-gamma receptors, and Down syndrome cells display significantly increased sensitivity to IFN action. We have previously reported that in utero anti-IFN IgG treatment of mice pregnant with trisomy 16 fetuses results in a significant improvement in trisomy 16 fetus growth and morphology and that anti-IFN-gamma IgG treatment can prevent the premature death of trisomy 16 fetal mouse cortical neurons in culture. We have now used IFN receptor subunit knockout mice to produce mouse fetuses that carry three No. 16 chromosomes and one copy each of disabled IFN-gamma receptor (IFNGR) and IFN-alpha/beta receptor (IFNAR-2) component genes. We report here that this partial IFN receptor knockout trisomy (PIRKOT) mouse fetus has significantly improved growth and yields cortical neurons whose viability is the equivalent of that seen in their euploid counterparts.
authors.affiliation: Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, IL 62794-9626, USA. lmaroun@siumed.edu
authors.forename: L E
authors.initials: LE
authors.lastname: Maroun
authors.forename: T N
authors.initials: TN
authors.lastname: Heffernan
authors.forename: D M
authors.initials: DM
authors.lastname: Hallam
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D002540:Cerebral Cortex / Q000473:pathology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009474:Neurons / Q000473:pathology; D010641:Phenotype; D011247:Pregnancy; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000235:genetics*; D014178:Translocation, Genetic; D014314:Trisomy; D000096743:Interferon gamma Receptor
chemical_list: D008565:Membrane Proteins; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C507964:IFNAR1 protein, human; C508034:Ifnar2 protein, mouse