Identification of the gene that, when mutated, causes the human obesity syndrome BBS4

Bardet-Biedl syndrome (BBS, MIM 209900) is a heterogeneous autosomal recessive disorder characterized by obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. The disorder is also associated with diabetes mellitus, hypertension, and congenital heart disease. Six distinct BBS loci map to 11q13 (BBS1), 16q21 (BBS2), 3p13-p12 (BBS3), 15q22.3-q23 (BBS4), 2q31 (BBS5), and 20p12 (BBS6). Although BBS is rare in the general population (<1/100,000), there is considerable interest in identifying the genes causing BBS because components of the phenotype, such as obesity and diabetes, are common. We and others have demonstrated that BBS6 is caused by mutations in the gene MKKS (refs. 12,13), mutation of which also causes McKusick-Kaufman syndrome (hydrometrocolpos, post-axial polydactyly, and congenital heart defects). MKKS has sequence homology to the alpha subunit of a prokaryotic chaperonin in the thermosome Thermoplasma acidophilum. We recently identified a novel gene that causes BBS2. The BBS2 protein has no significant similarity to other chaperonins or known proteins. Here we report the positional cloning and identification of mutations in BBS patients in a novel gene designated BBS4.     

Potentiating the diabetogenic effect of alloxan by N-sulphonyl-N-butylurea (BZ-55)

Zusammenfassung Es wird festgestellt, dass im voraus verabreichtes BZ-55 die diabetogene Wirkung des Alloxans bei Mäusen potenziert.     

Influence of previous feeding with a high-fat diet on liver steatosis produced by acute starvation or growth hormone in mice

Zusammenfassung Bei 12–22 Tage mit einer ausreichend ergänzten Fettdiät gefütterten Mäusen, tritt die durch akuten Hunger oder einmalige Verabfolgung von STH ausgelöste Lebersteatose, wenn überhaupt, nur in abgeschwächter Form auf. Dieser Effekt kann als Folgeerscheinung einer Stoffwechseladaptation an die hohe Fettzufuhr gedeutet werden, die durch eine gesteigerte Verwertungskapazität von exogenem und endogenem Fett in Erscheinung tritt.     

A double-stranded RNA binding protein required for activation of repressed messages in mammalian germ cells.

Chromatin packaging in mammalian spermatozoa requires an ordered replacement of the somatic histones by two classes of spermatid-specific basic proteins, the transition proteins and the protamines. Temporal expression of transition proteins and protamines during spermatid differentiation is under translational control, and premature translation of protamine 1 leads to precocious nuclear condensation and sterility. We have previously suggested that the double-stranded (ds) RNA binding protein Prbp (encoded by the gene Tarbp2) functions as a translational regulator during mouse spermatogenesis. Here we show that Prbp is required for proper translational activation of the mRNAs encoding the protamines. We generated mice that carry a targeted disruption of Tarbp2 and determined that they were sterile and severely oligospermic. Using immunohistological analysis, we determined that the endogenous Prm2 mRNA and a reporter mRNA carrying protamine 1 translational-control elements were translated in a mosaic pattern. We showed that failure to synthesize the protamines resulted in delayed replacement of the transition proteins and subsequent failure of spermiation. The timing of Prbp expression suggests that it may function as a chaperone in the assembly of specific translationally regulated ribonucleoprotein particles.     

Hämtologische Untersuchungen am SpitzhörnchenTupaia tana (Raffles 1821) (Tupaiidae,Prosimiae)

Summary The authors give the first results of hematological studies with Tree shrews (Tupaia tana) as compared with human blood, and an European hedgehog as a representative of the orderInsectivora. Counts of erythrocytes, leucocytes (including a differentiation of white cell types), and thrombocytes are dealt with together with an electrophoretic analysis of serum protein fractions.     

Teratogenic drugs inhibit tumour cell attachment to lectin-coated surfaces

Interactions between embryonic cells are generally thought to have a central role in the control of development. When these morphogenic interactions are interrupted by either physical intervention or genetic defects, normal development is impaired. In accord with these experiments, specific interactions between embryonic cells have been demonstrated in several in vitro systems. Many investigators have described homotypic aggregation of chick embryo cells, and heterotypic specificity has been described. Because of the importance of morphogenic cell-cell interactions in development it follows that agents that interfere with these interactions, regardless of the interference mechanism, are potential teratogens. Here we have used a simple in vitro cell to surface recognition system in an attempt to screen for potential teratogens. We have found a very high correlation between inhibitory activity in the in vitro assay and reported teratogenic activity in human or animal studies. This suggests that many teratogenic agents may act by interfering, in an as yet unknown way, in normal cell to cell interactions.     

Drug interactions in intestinal absorption of 3H-digitoxin in rats.

The absorption of 3H-digitoxin from perfused rat small intestine was inhibited by probenecid (1.0 x 10-2 M), ethacrynic acid (0.5 x 10-3 M), and mersalyl (8.0 x 10-3 M) indicating that digitoxin absorption is at least partly an active process.