title: Embryonic survival and severity of cardiac and craniofacial defects are affected by genetic background in fibroblast growth factor-16 null mice.
abstract: Disruption of the X-chromosome fibroblast growth factor 16 (Fgf-16) gene, a member of the FGF-9 subfamily with FGF-20, was linked with an effect on cardiac development in two independent studies. However, poor trabeculation with lethality by embryonic day (E) 11.5 was associated with only one, involving maintenance in Black Swiss (Bsw) versus C57BL/6 mice. The aim of this study was to examine the potential influence of genetic background through breeding the null mutation onto an alternate (C57BL/6) background. After three generations, 25% of Fgf-16(-/Y) mice survived to adulthood, which could be reversed by reducing the contribution of the C57BL/6 genetic background by back crossing to another strain. There was no significant difference between FGF-9 and FGF-20 RNA levels in Fgf-16 null versus wild-type mice regardless of strain. However, FGF-8 RNA levels were reduced significantly in Bsw but not C57BL/6 mice. FGF-8 is linked to anterior heart development and like the FGF-9 subfamily is reportedly expressed at E10.5. Like FGF-16, neuregulin as well as signaling via ErbB2 and ErbB4 receptors have been linked to trabeculae formation and cardiac development around E10.5. Basal neuregulin, ErbB2, and ErbB4 as well as FGF-8, FGF-9, and FGF-16 RNA levels varied in Bsw versus C57BL/6 mice. These data are consistent with the ability of genetic background to modify the phenotype and affect embryonic survival in Fgf-16 null mice.
authors.affiliation: Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada.
authors.forename: Shun Yan
authors.initials: SY
authors.lastname: Lu
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: Patricia
authors.initials: P
authors.lastname: Sheppard
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Bock
authors.forename: Farah
authors.initials: F
authors.lastname: Sheikh
authors.forename: Mary Lynn
authors.initials: ML
authors.lastname: Duckworth
authors.forename: Peter A
authors.initials: PA
authors.lastname: Cattini
mesh_terms: D000818:Animals; D019465:Craniofacial Abnormalities / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000378:metabolism*; D006331:Heart Diseases / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D014960:X Chromosome; D000075924:X-linked Nuclear Protein
chemical_list: C484686:Fgf16 protein, mouse; D009687:Nuclear Proteins; D005346:Fibroblast Growth Factors; D004265:DNA Helicases; C490462:Atrx protein, mouse; D000075924:X-linked Nuclear Protein