ABSTRACT. The rat autosomal dominant Rex (Re) mutation on chromosome 7 causes curly hair in Re/+ and hair loss in Re/Re rats. Histopathologically, the Re/+ rat showed dilatation of the hair follicle and hairs with irregularly-coated cuticles, and the Re/Re rat showed more severe effects. We identified Re as a 7-bp deletion at the splicing acceptor site of intron 1 of the keratin 71 (Krt71) gene, which is located within the Re critical chromosomal region and plays an important role in hair formation. The deletion provoked a 6-amino acid in-frame deletion (p.Val149_Gln154del) in the -helical rod domain of KRT71 protein. Identification of the Re mutation (Krt71 Re ) enables us to further understand the biological function of KRT71.

Pulmonary sclerosing hemangioma (SH) is an uncommon benign or low-grade malignant tumor. Multicentric SH and SH with lymph node metastasis have rarely been reported. The present report describes a case of pulmonary SH with lymph node metastasis in a middle-aged female. A nodule was found incidentally in the lower left lung. The patient underwent left lower pulmonary lobectomy and lymph node dissection. Histologically, the nodule demonstrated the characteristic features of SH and one of the resected lymph nodes contained a metastasis of this tumor. Thus, pulmonary SH has the potential to metastasize, a potential not suggested by histological features.

Cortical heterotopia, a malformation of the developing cortex, are a major cause of epilepsy and mental retardation in humans. Hemorrhagic hydrocephalus (hhy) mutation on mouse chromosome 12 results in subcortical heterotopia and nonobstructive hydrocephalus with frequent brain hemorrhage. Here, we show that coiled-coil domain-containing 85C (Ccdc85c), consisting of 6 exons that encode a 420 amino acid protein, is disrupted by replacement of a 3.2-kb sequence, including exon 2 in Ccdc85c by a 1.5-kb retrotransposon-like repeat sequence in the hhy mutant. Immunoreactivity to Ccdc85C was detected predominantly at the apical junctions of radial glia in the wall of lateral ventricles of the developing brain. In the hhy brain at embryonic (E) day 18 (E18), radial glial demise followed by agenesis of the ependymal layer lining the neonatal cortex and accumulation of neuronal specific nuclear protein (NeuN)-positive postmigratory neurons in the subcortical area occurred. Accumulation of E15-born, but not of E13-born, 5-bromo-2'-deoxyuridine labeled neurons expressing special AT-rich sequence binding protein 2 was detected in both heterotopia and the superficial layers of the hhy neocortex at postnatal day 7. Ccdc85c deficiency permitted radial scattering of paired box gene 6-positive neural progenitors in the ventricular zone, likely resulting in reduced self-renewal of the progenitors in the developing hhy cortex. These findings indicate an important role of Ccdc85C in cortical development and provide a mouse model to study pathogenesis of subcortical heterotopia and hydrocephalus.

It has been reported that anaplastic lymphoma kinase (ALK) protein is expressed in a proportion of non-small-cell carcinomas (mainly adenocarcinomas). By contrast, high-sensitivity immunohistochemistry (IHC) rarely detects ALK protein expression in neuroendocrine carcinomas (NECs) of the lung, which include small-cell carcinomas and large-cell neuroendocrine carcinomas (LCNECs). We herein present a case of NEC that was identified as ALK-positive via high-sensitivity IHC. A 51-year-old man was diagnosed with small-cell carcinoma in the upper lobe of the right lung. Although high-sensitivity IHC revealed that the tumor weakly expressed the ALK protein, no fusion gene with ALK was found using fluorescence in situ hybridization (FISH). Standard chemotherapy was administered to the patient. Six months after the first visit to the hospital for the tumor, another tumor was identified in the upper lobe of the left lung. The tumor was resected and diagnosed as NEC displaying LCNEC-like characteristics. This NEC also moderately expressed ALK protein by high-sensitivity IHC, without exhibiting fusion genes with ALK on FISH. These data suggest that the presence of ALK fusion genes should be confirmed by FISH or reverse transcription polymerase chain reaction, even if high-sensitivity IHC for ALK protein is positive in lung cancer.