Loss of MeCP2 in the rat models regression, impaired sociability and transcriptional deficits of Rett syndrome.

Mouse models of the transcriptional modulator Methyl-CpG-Binding Protein 2 (MeCP2) have advanced our understanding of Rett syndrome (RTT). RTT is a 'prototypical' neurodevelopmental disorder with many clinical features overlapping with other intellectual and developmental disabilities (IDD). Therapeutic interventions for RTT may therefore have broader applications.

Fmr1 and Nlgn3 knockout rats: novel tools for investigating autism spectrum disorders.

Animal models are critical for gaining insights into autism spectrum disorder (ASD). Despite their apparent advantages to mice for neural studies, rats have not been widely used for disorders of the human CNS, such as ASD, for the lack of convenient genome manipulation tools. Here we describe two of the first transgenic rat models for ASD, developed using zinc-finger nuclease (ZFN) methodologies, and their initial behavioral assessment using a rapid juvenile test battery.

A simple statistical test to infer the causality of target/phenotype correlation from small molecule phenotypic screens.

Motivation: Cell-based phenotypic screens using small molecule inhibitors is an important technology for early drug discovery if the relationship between the disease-related cellular phenotype and inhibitors' biological targets can be determined. However, chemical inhibitors are rightfully believed to be less specific than perturbation by biological agents, such as antibody and small inference RNA. Therefore, it is often a challenge in small molecule phenotypic screening to infer the causality between a particular cellular phenotype and the inactivation of the responsible protein due to the off-target effect of the inhibitors.

Modifying behavioral phenotypes in Fmr1KO mice: genetic background differences reveal autistic-like responses.

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in humans. In addition to cognitive impairment, patients may exhibit hyperactivity, attention deficits, social difficulties and anxiety, and autistic-like behaviors. The degree to which patients display these behaviors varies considerably and is influenced by family history, suggesting that genetic modifiers play a role in the expression of behaviors in FXS.

Multiple autism-like behaviors in a novel transgenic mouse model.

Autism spectrum disorder (ASD) diagnoses are behaviorally based with no defined universal biomarkers, occur at a 1:110 ratio in the population, and predominantly affect males compared to females at approximately a 4:1 ratio. One approach to investigate and identify causes of ASD is to use organisms that display abnormal behavioral responses that model ASD-related impairments. This study describes a novel transgenic mouse, MALTT, which was generated using a forward genetics approach.

Three-dimensional solution structure of the calcium-signaling protein apo-S100A1 as determined by NMR.

S100A1, a member of the S100 protein family, is an EF-hand containing Ca(2+)-binding protein (93 residues per subunit) with noncovalent interactions at its dimer interface. Each subunit of S100A1 has four alpha-helices and a small antiparallel beta-sheet consistent with two helix-loop-helix calcium-binding domains [Baldiserri et al. (1999) J.