Sex-Dependent Novelty Response in Neurexin-1α Mutant Mice

Neurexin-1 alpha (NRXN1α) belongs to the family of cell adhesion molecules (CAMs), which are involved in the formation of neuronal networks and synapses. NRXN1α gene mutations have been identified in neuropsychiatric diseases including Schizophrenia (SCZ) and Autism Spectrum Disorder (ASD). In order to get a better understanding of the pleiotropic behavioral manifestations caused by NRXN1α gene mutations, we performed a behavioral study of Nrxn1α heterozygous knock-out (+/−) mice and observed increased responsiveness to novelty and accelerated habituation to novel environments compared to wild type (+/+) litter-mates. However, this effect was mainly observed in male mice, strongly suggesting that gender-specific mechanisms play an important role in Nrxn1α-induced phenotypes

Sex-dependent novelty response in neurexin-1α mutant mice.

Neurexin-1 alpha (NRXN1α) belongs to the family of cell adhesion molecules (CAMs), which are involved in the formation of neuronal networks and synapses. NRXN1α gene mutations have been identified in neuropsychiatric diseases including Schizophrenia (SCZ) and Autism Spectrum Disorder (ASD). In order to get a better understanding of the pleiotropic behavioral manifestations caused by NRXN1α gene mutations, we performed a behavioral study of Nrxn1α heterozygous knock-out (+/-) mice and observed increased responsiveness to novelty and accelerated habituation to novel environments compared to wild type (+/+) litter-mates. However, this effect was mainly observed in male mice, strongly suggesting that gender-specific mechanisms play an important role in Nrxn1α-induced phenotypes

An improved procedure for integrated behavioral z-scoring illustrated with modified Hole Board behavior of male inbred laboratory mice

Background Guilloux et al. introduced: integrated behavioral z-scoring, a method for behavioral phenotyping of mice. Using this method multiple ethological variables can be combined to show an overall description of a certain behavioral dimension or motivational system. However, a problem may occur when the control group used for the calculation has a standard deviation of zero or when no control group is present to act as a reference group. New method In order to solve these problems, an improved procedure is suggested: taking the pooled data as reference. For this purpose a behavioral study with male mice from three inbred strains was carried out. The integrated behavioral z-scoring methodology was applied, thereby taking five different reference group options. The outcome regarding statistical significance and practical importance was compared. Results Significant effects and effect sizes were influenced by the choice of the reference group. In some cases it was impossible to use a certain population and condition, because one or more behavioral variables in question had a standard deviation of zero. Based on the improved method, male mice from the three inbred strains differed regarding activity and anxiety. Comparison with existing method Taking the method described by Guilloux et al. as basis, the present procedure improved the generalizability to all types of experimental designs in animal behavioral research. Conclusions To solve the aforementioned problems and to avoid getting the diagnosis of data manipulation, the pooled data (combining the data from all experimental groups in a study) as reference option is recommended

Habituation was described by the difference between trial 3 and trial 1, determined for the total distance moved in the open field (A) and the total time spend in the center of the open field test (B).

<p>Error bars are standard errors of the mean. P-values of less than 0.050 shows significant effects, while p-values between 0.050 and 0.100 indicate a trend.</p

Representation of open field movement tracking pattern measured in individual male and female WT(+/+) and heterozygous KO(+/−) mice in three consecutive 5 minute trials.

<p>Representation of open field movement tracking pattern measured in individual male and female WT(+/+) and heterozygous KO(+/−) mice in three consecutive 5 minute trials.</p

Total distance moved in the open field arena in cm (A) and total time spend in the center of the open field in seconds (B) were measured in the open field test in male and female heterozygous KO(+/−) and WT(+/+) mice (mean +/− SEM).

<p>Alpha was set at 0.0167 after Bonferroni correction.</p

Object discrimination was measured by the relative time male mice spend exploring the novel (unknown) object.

<p>Significant longer exploration of the novel object compared to the 50% coincidence level indicates recognition of the novel object compared to the familiar one (group mean +/− SEM).</p