Association of TUSC3 gene polymorphisms with non-syndromic mental retardation based on nuclear families in the Qinba mountain area of China.

TUSC3 interacts with the protein phosphatase 1 and magnesium ion transport system, which plays an important role in learning and memory. Abnormal conditions of learning and memory are common clinical characteristics of mental retardation (MR). However, the association of TUSC3 genetic polymorphisms with MR remains unknown. A total of 456 DNA samples including 174 nuclear families containing MR were collected in the Qinba mountain area of China. The genotypes of eight tag single nucleotide polymorphisms of TUSC3 were evaluated with traditional genetic methods. Family-based association tests, transmission disequilibrium tests (TDTs), and haplotype relative risk (HRR) analyses were performed to investigate the association between genetic variants of the TUSC3 gene and MR. The genetic polymorphisms rs10093881, rs6530893, and rs6994908 were associated with MR (all P values <0.05) based upon the results of single-site TDT and HRR analyses. The haplotype block consisting of rs6530893 and rs6994908, harboring the sixth exon of TUSC3, was also associated with MR (all P values <0.05). This study demonstrated an association between genetic polymorphisms of the TUSC3 gene and MR in the Qinba mountain area, the sixth exon of which might contribute to the risk of MR. However, further studies are needed on the causal mechanisms in this association.

No association between FGD1 gene polymorphisms and intellectual developmental disability in the Qinba mountain area.

FGD1 encoding a guanine nucleotide exchange factor, specifically activates Rho GTPase cell division cycle 42 (Cdc42). Dysfunction of FGD1 causes Aarskog-Scott syndrome (MIM #305400), an X-linked disorder that may affect bone and intellectual development. However, the relationship between FGD1 and intellectual developmental disorders (IDD) remains unclear. The purpose of this study was to investigate the genetic association between the FGD1 polymorphism and IDD. Working with families from the Qinba mountain area where the occurrence of IDD is higher than the average in China, we analyzed 456 samples from 130 nuclear families, effectively controlling for stratification and environmental factors. Five SNP loci (rs2230265, rs7881608, rs2239809, rs6614244, and rs2284710) were selected that were well distributed within the FGD1 gene. Genotyping was performed through single-strand conformation polymorphism and restriction fragment length polymorphism. The data were analyzed with transmission disequilibrium tests. In the Qinba mountain area, no significant association was observed between IDD and allele or genotype frequencies, or the haplotype of the 5 SNP loci of the FGD1 gene. The results indicate that FGD1 may not be a monogenetic X-linked factor in IDD. Further studies are required to investigate its role in intellectual development based on its specific interactions with Cdc42 or other partner proteins contributing to IDD.

Molecular adjuvant interleukin-33 enhances the antifertility effect of Lagurus lagurus zona pellucida 3 DNA vaccine administered by the mucosal route.

It has been shown that cytokines can act as molecular adjuvant to enhance the immune response induced by DNA vaccines, but it is unknown whether interleukin 33 (IL-33) can enhance the immunocontraceptive effect induced by DNA vaccines. In the present study, we explored the effects of murine IL-33 on infertility induced by Lagurus lagurus zona pellucida 3 (Lzp3) contraceptive DNA vaccine administered by the mucosal route. Plasmid pcD-Lzp3 and plasmid pcD-mIL-33 were encapsulated with chitosan to generate the nanoparticle chi-(pcD-Lzp3+pcD-mIL-33) as the DNA vaccine. Sixty female ICR mice, divided into 5 groups (n=12/group), were intranasally immunized on days 0, 14, 28, and 42. After intranasal immunization, the anti-LZP3-specific IgG in serum and IgA in vaginal secretions and feces were determined by ELISA. The results showed that chi-(pcD-Lzp3+pcD-mIL-33) co-immunization induced the highest levels of serum IgG, secreted mucosal IgA, and T cell proliferation. Importantly, mice co-immunized with chi-(pcD-Lzp3+pcD-mIL-33) had the lowest birth rate and mean litter size, which correlated with high levels of antibodies. Ovaries from infertile female mice co-immunized with chi-(pcD-Lzp3+pcD-mIL-33) showed abnormal development of ovarian follicles, indicated by atretic follicles and loss of oocytes. Our results demonstrated that intranasal delivery of the molecular adjuvant mIL-33 with chi-pcD-Lzp3 significantly increased infertility by enhancing both systemic and mucosal immune responses. Therefore, chi-(pcD-Lzp3+pcD-mIL-33) co-immunization could be a strategy for controlling the population of wild animal pests.

Molecular adjuvant interleukin-33 enhances the antifertility effect of Lagurus lagurus zona pellucida 3 DNA vaccine administered by the mucosal route

It has been shown that cytokines can act as molecular adjuvant to enhance the immune response induced by DNA vaccines, but it is unknown whether interleukin 33 (IL-33) can enhance the immunocontraceptive effect induced by DNA vaccines. In the present study, we explored the effects of murine IL-33 on infertility induced by Lagurus lagurus zona pellucida 3 (Lzp3) contraceptive DNA vaccine administered by the mucosal route. Plasmid pcD-Lzp3 and plasmid pcD-mIL-33 were encapsulated with chitosan to generate the nanoparticle chi-(pcD-Lzp3+pcD-mIL-33) as the DNA vaccine. Sixty female ICR mice, divided into 5 groups (n=12/group), were intranasally immunized on days 0, 14, 28, and 42. After intranasal immunization, the anti-LZP3-specific IgG in serum and IgA in vaginal secretions and feces were determined by ELISA. The results showed that chi-(pcD-Lzp3+pcD-mIL-33) co-immunization induced the highest levels of serum IgG, secreted mucosal IgA, and T cell proliferation. Importantly, mice co-immunized with chi-(pcD-Lzp3+pcD-mIL-33) had the lowest birth rate and mean litter size, which correlated with high levels of antibodies. Ovaries from infertile female mice co-immunized with chi-(pcD-Lzp3+pcD-mIL-33) showed abnormal development of ovarian follicles, indicated by atretic follicles and loss of oocytes. Our results demonstrated that intranasal delivery of the molecular adjuvant mIL-33 with chi-pcD-Lzp3 significantly increased infertility by enhancing both systemic and mucosal immune responses. Therefore, chi-(pcD-Lzp3+pcD-mIL-33) co-immunization could be a strategy for controlling the population of wild animal pests.