Increased lambda(perpendicular) with no significant change in lambda(parallel) appears to characterize noncystic WM injury with reduced myelination, whereas reduction in both lambda(parallel) and lambda(perpendicular) characterize severe damage with loss of structural integrity and necrosis. Combining with FA and trace, lambda(parallel) and lambda(perpendicular) provide additional information which reflects type and severity of HI injury.

Cataract is the most common cause of visual loss in humans. A spontaneously occurred, autosomal dominant mouse mutant Secc, which displayed combined features of small eye, cataract and closed eyelid was discovered in our laboratory. In this study, we identified the mutation and characterized the cataract phenotype of this novel Secc mutant. The Secc mutant mice have eyelids that remain half-closed throughout their life. The mutant lens has a significant reduction in size and with opaque spots clustered in the centre. Histological analysis showed that in the core region of the mutant lens, the fiber cells were disorganized and clefts and vacuoles were observed. The cataract phenotype was evident from new born stage. We identified the Secc mutation by linkage analysis using whole genome microsatellite markers and SNP markers. The Secc locus was mapped at chromosome 1 flanked by SNPs rs3158129 and rs13475900. Based on the chromosomal position, the candidate cataract locus γ-crystallin gene cluster (Cryg) was investigated by sequencing. A single base deletion (299delG) in exon 3 of Cryga which led to a frame-shift of amino acid sequence from position 91 was identified. As a result of this mutation, the sequences of the 3rd and 4th Greek-key motifs of the γA-crystallin are replaced with an unrelated C-terminal peptide of 75 residues long. Coincidentally, the point mutation generated a HindIII restriction site, allowing the identification of the CrygaSecc mutant allele by RFLP. Western blot analysis of 3-week old lenses showed that the expression of γ-crystallins was reduced in the CrygaSecc mutant. Furthermore, in cell transfection assays using CrygaSecc mutant cDNA expression constructs in 293T, COS-7 and human lens epithelial B3 cell lines, the mutant γA-crystallins were enriched in the insoluble fractions and appeared as insoluble aggregates in the transfected cells. In conclusion, we have demonstrated that the Secc mutation leads to the generation of CrygaSecc proteins with reduced solubility and prone to form aggregates within lens cells. Accumulation of mutant proteins in the lens fibers would lead to cataract formation in the Secc mutant.

nectin-1 gene are responsible for a rare human syndrome characterized by ectodermal dysplasia (ED). The nectin-1 (N1) null mutant mice have a mild defect in skin, (Wakamatsu etal., 2007), but no severe phenotypes were reported, suggesting the compensation by other nectins. In this study, we tested this hypothesis by generating N1 and N3 compound mutant mice.We observed coexpression of N1 and N3 in the inner root sheath of hair follicles and in the suprabasal layer of epidermis.All compound mutants showed severe skin abnormality and reduced hair follicles at post natal day 10. Histological analysis indicated that the compound mutant skin was eosinophilic and the nuclei in the basal cell layer exhibited abnormal shapes and arrangement. Their hair follicles were smaller than wild type and had lost their typical structure. Immunohistochemical analysis revealed that the basal cell layer marker laminin, as well as filaggrin and loricrin were severely reduced in the mutant skin, and that keratin14 was reduced while the expression keratin 10 was normal. The cell junction molecules E-cadherin, ZO-1, and DSG were reduced or mislocalized, and the expression of p63 and Ki67 were severely reduced in the mutant skin. Similar gene expression alterations were also observed in the mutant hair follicles.These results indicate that N1 and N3 have important functions in the control of epidermal homeostasis and hair formation and that they are functionally redundant in these processes. Down syndrome is characterised by trisomy of chromosome 21, and has been linked to overexpression of a number of genes located in the Down Syndrome Critical Region on chromosome 21. DYRK1A is one of the genes in the DSCR and DYRK family members have been shown to play a critical role in the development of the nervous system in worms, mouse and drosophila. Overexpression of active GFP-DYRK1A in HeLa cells causes centrosome duplication and defects in mitotic spindle structure, consistent with a role in mitotic function. To date, there is no clear definition of how DYRK1A functions in cycling cells or in neurogenesis and constitutes an important biological and medical question.We are examining the role of DYRK1A in cell division and in neurogenesis in cultured cells and in the developing spinal cord.We use HeLa cells to probe the subcellular details of DYRK1A function and a novel imaging-based assay that monitors cells within the early chick spinal cord as they form mitotic spindles, transit mitosis and give rise to neurons or neural progenitors.We have shown that the endogenous DYRK1A and the overexpression of kinase and carboxy terminus domains localise to centrosomes. We have also found that depleting DYRK1A by siRNAs causes a loss of metaphase cells, an increase in sub-G1 cells, and delocalization of PLK1 from the midbody. Having shown a requirement for DYRK1A in mitosis, we aim to understand the link between a fundamental requirement in cell division and the fundamental processes of cell differentiation.A novel syndrome causing hereditary birth def...

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