Loss of PIDD limits NF-κB activation and cytokine production but not cell survival or transformation after DNA damage.

Activation of NF-κB (nuclear factor of kappa light chain gene enhancer in B cells) in response to DNA damage is considered to contribute to repair of genetic lesions, increased cell survival and cytokine release. The molecular mechanisms orchestrating this cytoplasmic event involve core components of the nuclear DNA damage response machinery, including ATM-kinase (ataxia telangiectasia mutated kinase) and PARP-1 (poly (ADP-ribose) polymerase 1). The physiological consequences of defective NF-κB activation in this context, however, remain poorly investigated. Here we report on the role of the 'p53-induced protein with a death domain', PIDD, which appears rate limiting in this process, as is PARP-1. Despite impaired NF-κB activation, DNA damage did not increase cell death or reduce clonal survival of various cell types lacking PIDD, such as mouse embryonic fibroblasts or stem and progenitor cells of the hematopoietic system. Furthermore, lymphomagenesis induced by γ-irradiation (IR) was unaffected by deficiency for PIDD or PARP-1, indicating that loss of DNA damage-triggered NF-κB signalling does not affect IR-driven tumorigenesis. However, loss of either gene compromised cytokine release after acute IR injury. Hence, we propose that NF-κB's most notable function after DNA damage in primary cells is related to the release of cytokines, thereby contributing to sterile inflammation.

Mutagenic transgene insertion into a region of high gene density and multiple linkage disruptions on mouse chromosome 11.

We have characterized a 185-kb contig surrounding a transgene on distal mouse chromosome 11, the insertion of which has caused a recessive phenotype with skeletal malformations. By cDNA selection and sequencing we have found six genes (Lasp1, Rpl23, Mllt6, Pip5k2b, Psmb3, Zfp144), one truncated gene (Mel13), and one pseudogene (Rps15-ps) within this region. The murine Mllt6 gene is new, it was identified by its high homology (90% identity) with the human homologue MLLT6. Psmb3 and Pip5k2b had not yet been assigned to mouse chromosomes. A comparison with the corresponding region on human chromosome 17q12 revealed several small-scale rearrangements during evolutionary divergence within this cluster of densely packed genes.

Genomic organization and chromosome location of the murine Rpl23 gene.

The mouse gene coding for ribosomal protein L23 (Rpl23) has been fully sequenced, including 580 bp of the 5' upstream region. The 5-kb gene comprises 5 exons and contains an unusually long (3,153 bp) third intron. The gene was mapped to the distal region of mouse chromosome 11, homologous to human chromosome 17q21-->q22.

Microvascularization of the pineal gland in the freshwater turtle, Pseudemys scripta elegans (Reptilia): a scanning electron microscopic study of vascular corrosion casts.

Gross supply, microvascular patterns, and drainage routes of the pineal gland and its vascular relations with associated structures (dorsal sac, paraphysis, choroid plexus of the third ventricle) were studied by scanning electron microscopy of microvascular corrosion casts in 10 specimens of the freshwater turtle, Pseudemys scripta elegans. Light microscopy of tissue sections (one transverse and one longitudinal series) served to attribute cast vascular territories to anatomical structures. The tubular pineal gland body is supplied bilaterally by small branches of the saccular artery, a branch of the lateral choroidal artery. Branches of the diencephalic artery supply the pineal stalk. The pineal gland microvascular bed is a two-dimensional network that embraces the tubular gland. The network is made up mainly of venules with few true capillaries. Venules draining the ventral surface of the pineal gland body join those coming from the choroid plexus of the third ventricle and drain into the sagittal sinus. The less dense vascular network embracing the dorsal surface of the pineal body drains directly into the sagittal sinus. The pineal stalk drains into the diencephalic vein or directly into the sagittal sinus. No efferent (venous) vascular connections capable as transport route for pineal secretions toward surrounding telencephalic, diencephalic, or mesencephalic areas were found.

Microvascularization of the cerebellum in the turtle, Pseudemys scripta elegans (Reptilia). A scanning electron microscope study of microvascular corrosion casts, including stereological measurements.

Cerebellar blood supply and microvascular patterns were studied in 12 freshwater turtles Pseudemys scripta elegans by scanning electron microscopy (SEM) of microvascular corrosion casts and histology. Vascular densities were estimated by point counting methods from casts and thin sections (7 microns). Short A2-arterioles and recurrent branches from A3-arterioles supply the capillary bed of the molecular layer, while V2 and V3 venules drain it. The Purkinje cell layer is supplied by horizontal branches ("parallel arteries") of A4 and A3 arterioles, which capillarize toward the granular and molecular layers. V2, V3 and V4 venules drain the areas supplied by A3 arterioles. The deep granular and subependymal layers are supplied by A4 arterioles, those adjacent to the Purkinje cell layer also by A3 arterioles. The areas supplied by A4 arterioles drain via V4 venules. The granular and Purkinje cell layers taken together have an estimated vascular density of 4.1%, while in the molecular layer this value is 3.3%. Our findings largely confirm published data from Testudo geometrica and Pseudemys scripta elegans with respect to gross supply and drainage. The microvascular patterns are similar to those of the human cerebellar cortex, particularly the basic patterns of intracortical arterioles and venules. The molecular layer, like that in the human brain, has a circulatory bed largely independent of that of the Purkinje cell and granular layers. In contrast to the human brain, a cerebellar pial capillary network is present in the brain of the turtle.