The disks of vertebrate photoreceptors are produced by outgrowths of the plasma membrane. Hence genes that encode retinal proteins targeted to plasma membrane protrusions represent candidates for inherited retinal degenerations. One such candidate is the gene encoding human prominin (mouse)-like 1 (PROML1, previously known as AC133 antigen) which belongs to the prominin family of 5-transmembrane domain proteins. Murine prominin (prom) shows a strong preference for plasma membrane protrusions in a variety of epithelial cells whereas PROML1 is expressed in retinoblastoma cell lines and adult retina. In the present study, molecular genetic analyses of a pedigree segregating for autosomal recessive retinal degeneration indicated that the affected individuals were homozygous for a nucleotide 1878 deletion in PROML1. This alteration is predicted to result in a frameshift at codon 614 with premature termination of translation. Expression of a similar prom deletion mutant in CHO cells indicated that the truncated protein does not reach the cell surface. Immunocytochemistry revealed that prom is concentrated in the plasma membrane evaginations at the base of the outer segments of rod photoreceptors. These findings suggest that loss of prominin causes retinal degeneration, possibly because of impaired generation of the evaginations and/or impaired conversion of the evaginations to disks.

The transcription factors Sox4 and Sox11 are important regulators of diverse developmental processes including heart, lung, pancreas, spleen, and B-cell development. Here we have studied the role of the related Sox12 as the third protein of the SoxC group both in vivo and in vitro. Despite widespread Sox12 expression during embryonic development, Sox12-deficient mice developed surprisingly normally, so that they were born alive, showed no gross phenotypic abnormalities, and were fertile in both sexes. Comparison with the related Sox4 and Sox11 revealed extensive overlap in the embryonic expression pattern but more uniform expression levels for Sox12, without sites of particularly high expression. All three Sox proteins furthermore exhibited comparable DNA-binding characteristics and functioned as transcriptional activators. Sox12 was, however, a relatively weak transactivator in comparison to Sox11. We conclude that Sox4 and Sox11 function redundantly with Sox12 and can compensate its loss during mouse development. Because of differences in expression levels and transactivation rates, however, functional compensation is not reciprocal.

Siglec-H is a key negative regulator of the type I interferon pathway, reducing the incidence of autoimmunity after viral infection.