Abstract
Stathmin 1 (STMN1) is a neuronal growth-associated protein that is involved in microtubule dynamics and plays an important role in synaptic outgrowth and plasticity. Given that STMN1 affects fear behavior, we hypothesized that genetic variations in the STMN1 transcriptional regulatory region affect gene transcription activity and control fear behavior. In this study, two single nucleotide polymorphisms (SNPs), g. -327 A>G and g. -125 C>T, were identified in 317 English Springer Spaniels. A bioinformatics analysis revealed that both were loci located in the canine STMN1 putative promoter region and affected transcription factor binding. A statistical analysis revealed that the TT genotype at g.-125 C>T produced a significantly greater fear level than that of the CC genotype (P < 0.05). Furthermore, the H4H4 (GTGT) haplotype combination was significantly associated with canine fear behavior (P < 0.01). Using serially truncated constructs of the STMN1 promoters and the luciferase reporter, we found that a 395 bp (−312 nt to +83 nt) fragment constituted the core promoter region. The luciferase assay also revealed that the H4 (GT) haplotype promoter had higher activity than that of other haplotypes. Overall, our results suggest that the two SNPs in the canine STMN1 promoter region could affect canine fear behavior by altering STMN1 transcriptional activity.
Highlights
Police dogs play a unique role in preventing and cracking down on crime [1]
The RT-qPCR assay revealed that the high-fear level group expressed higher Stathmin 1 (STMN1) mRNA levels than those of the low-fear level group (P < 0.05) in the amygdala, medial prefrontal cortex (mPFC), and hippocampus (Fig 1B), but not in the brainstem
A significant correlation was detected between STMN1 mRNA levels in the amygdala, mPFC, and hippocampus and fear behavior of the dogs
Summary
Police dogs play a unique role in preventing and cracking down on crime [1]. In the Nanjing Police Dog Institute of the Ministry of Public Security of the People’s Republic of China, the training records of English Springer Spaniels show that many puppies are unable to be trained into working dogs because they are fearful. Fear can be affected by genetic, environmental. STMN1 Affect Fear Behavior of English Springer Spaniel [2, 3] (or their interaction) and epigenetic factors [4]. Fear can protect the dog by defensive behavior or escape once it perceived danger [5, 6]. Fearful behavior in dogs can be assessed by objective behavioral testing or subjective questionnaire surveys. Few differences are found between behavioral tests and questionnaire surveys in the consistency of assessing the fearfulness of a dog [15,16,17]. The genetic background of fear is polygenic and most likely involves genes associated with different cellular processes and pathways, but the specifics remain unclear [18]. Further studies to identify specific genes involved in the formation and expression of fear are needed
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