title: Low-anxiety rat phenotypes can be further reduced through genetic intervention.
abstract: BACKGROUND
  A previous study using an intercross between the inbred rat strains Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) identified a locus on chromosome 4, named Anxrr16, influencing an experimental index of anxiety and showing a transgressive effect, with alleles from the LEW strain (more anxious) decreasing rather than increasing anxiety.
  
  
  OBJECTIVE
  To confirm the location and isolate the effect of a rat genome region named Anxrr16 through a planned genomic recombination strategy, where the target locus in SHR rats was replaced with LEW genetic material.
  
  
  METHODS
  A new congenic strain, named SHR.LEW-Anxrr16 (SLA16), was developed from a cross between LEW (donor) and SHR (receptor) rats and then evaluated in several anxiety-related tests. The activity and attention levels of the new strain were also evaluated, since hyperactivity was observed during its construction and because SHR is a model of attention deficit hyperactivity disorder.
  
  
  RESULTS
  Significant effects of Anxrr16 were found for open field central locomotion, as well as for other indices of anxiety from the light/dark box, triple test and T-maze. In all cases, the low-anxiety levels of SHR rats were further reduced by the insertion of LEW alleles. Differences in locomotor activity were found only in unfamiliar (hence stressful) environments and no genetic effects were observed in indices of attention.
  
  
  CONCLUSIONS
  The SLA16 strain can help in the identification of the molecular pathways involved in experimental anxiety and it demonstrates how apparently extreme phenotypes sometimes hide major opposite-acting genes.
authors.affiliation: Laboratório de Genética do Comportamento, Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Gabriela Ferreira
authors.initials: GF
authors.lastname: de Medeiros
authors.affiliation: Laboratório de Genética do Comportamento, Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Elayne
authors.initials: E
authors.lastname: Pereira
authors.affiliation: Laboratório de Genética do Comportamento, Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Natalli
authors.initials: N
authors.lastname: Granzotto
authors.affiliation: Laboratório de Genética do Comportamento, Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Ramos
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000503:physiopathology*; D001522:Behavior, Animal; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D030762:Estrous Cycle; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D008297:Male; D009043:Motor Activity / Q000235:genetics; D010641:Phenotype; D040641:Quantitative Trait Loci; D051381:Rats; D011995:Recombination, Genetic