Harlequin ichthyosis (ichq): a juvenile lethal mouse mutation with ichthyosiform dermatitis.

The harlequin ichthyosis (ichq) mouse mutation arose spontaneously in 1989 in a colony of BALB/cJ mice at The Jackson Laboratory. Affected mice developed thick skin due to formation of compact, orthokeratotic scales that fractured over articular surfaces, secondary to bending. Harlequin ichthyosis mice on the inbred BALB/cJ background died between 9 and 12 days of age. Onset of the clinical phenotype corresponded with emergence of hair fibers from follicles at 5 days of age. There was marked proliferation of the root sheaths of anagen hair follicles, limited to the region within the dermis. Sebaceous glands were present but small compared with those of littermate controls. Emerging hair fibers were surrounded by a thick, compact sheath of cornified cells. Mutant skin contained large mitochondria with lamellar-shaped, electron-dense structures at the ultrastructural level. Keratohyalin granules were smaller and less pleomorphic than those in control mice. Lamellar bodies were not evident in either mutant or littermate control mice. Using a panel of antibodies to evaluate changes in keratinocyte differentiation, mouse-specific keratin 6 was overexpressed in the suprabasilar, hyperplastic epidermis. Loricrin expression, within the cytoplasm of cells in the stratum granulosum, decreased rapidly postmortem, unlike that in normal mice where it was stable for over 24 hours postmortem. Filaggrin expression, within granules of cells in the stratum granulosum, was prominent, corresponding to hypergranulosis evident by light microscopy in mutant mouse skin. Skin grafts from harlequin ichthyosis mice grafted onto immunodeficient nude mice maintained the phenotype for the 10-week observation period. The mutant gene locus mapped to the proximal end of mouse chromosome 19 and is inherited as a fully penetrant autosomal recessive gene. The harlequin ichthyosis mouse mutation is very similar to human type 2 harlequin ichthyosis for which it may be a good model.     

Prenatal ultrasound diagnosis of clubfoot

Five cases of congenital clubfoot diagnosed prenatally by ultrasound are reported. The incidence of clubfoot may be higher within an affected family and may be associated with other structural anomalies or chromosomal abnormalities. Identifying a clubfoot in utero should therefore alert the sonographer that other anomalies may be present and should lead to a detailed structural survey.     

The detection of pollutant impact in marine environments: Condition index, oxidative DNA damage, and their associations with metal bioaccumulation in the Sydney rock oyster Saccostrea commercialis

Specimens of the Sydney rock oyster Saccostrea commercialis were deployed for a 3-month period at control and sewage disturbed marine locations in the Hunter Region, New South Wales, Australia. The DNA damage product, 8-hydroxyguanine, was measured by GC/MS-SIM from chromatin extracts of the gill tissues of oysters to assess oxidative damage. The levels ranged from 11.5 to 18.8 modified bases per 10⁷ guanine bases. Although the condition indices were significantly different between the Redhead control site (178.3±3.6) and the Burwood sewage disturbed location (140.4±4.4), no significant differences in 8-hydroxyguanine concentrations were detected between the sites, and the concentration of 8-hydroxyguanine was not correlated to condition index. However, levels of the DNA base modification were correlated with the concentrations of bioaccumulated lead (r=0.84, P=0.036). This association provides in vivo evidence that the bioaccumulation of lead results in oxidative damage to DNA. An additional control and sewage disturbed site were included to investigate the relationship between heavy metal bioaccumulation and the condition index of deployed oysters. After the 3-month deployment period, the condition index was negatively correlated to concentrations of bioaccumulated mercury (r=–0.80, P<0.001), cobalt (r=–0.65, P<0.01), and nickel (r=–0.69, P<0.01), suggesting a strong negative influence of these metals at relatively low concentrations on the physiological condition of the oysters.