Mapping anti-müllerian hormone (Amh) and related sequences in the mouse: identification of a new region of homology between MMU10 and HSA19p.

A panel of 78 backcross progeny, BALB/cJ x (BALB/cJ x CAST/Ei)F1, was used to map the gene encoding anti-Müllerian hormone (Amh), also called Müllerian inhibiting substance, to mouse Chromosome 10 (MMU10). This analysis identified a new region of linkage homology between human Chromosome 19p (HSA 19p) and MMU10 and localized an apparent recombinational hot spot in (C57BL/6J x Mus spretus)F1 females [compared with (BALB/cJ x CAST/Ei)F1 males] to the interval between phenylalanine hydroxylase (Pah) and mast cell growth factor (Mgf). In addition, eight unlinked polymorphic sequences, provisionally designated Amh-related sequences (Amh-rs1 through Amh-rs8), were identified by Southern blot analysis using Amh probes. Amh-rs1, -rs2, -rs4, and -rs7 were mapped to MMU1, 13, 12, and 15, respectively, by recombinant inbred (RI) strain and intraspecific backcross analyses. The NXSM RI strain distribution patterns for the four unmapped loci are also presented.     

XY female mice express H-Y antigen

Karyotypically XY individuals of the C57BL/6J-Y^POS mouse stock develop as females or hermaphrodites, but never as normal males. The aberrant sexual development results from the interaction of the C57BL/6J genetic background with the M. poschiavinus-derived Y chromosome. XY females from this stock were assayed for H-Y antigen. By the criteria of skin-grafting, the cell-mediated lympholysis test, and the popliteal lymph node assay, these XY females are antigenically indistinguishable from normal C57BL/6 males. Implications for the hypothesis that H-Y antigen induces formation of the mammalian testis are discussed.     

Late replication patterns in adult and embryonic mice carrying Searle's X-autosome translocation

Bromodeoxyuridine-dye technique analysis of X chromosome DNA synthesis in female adult and fetal mice carrying the balanced form of the T(X; 16) 16H translocation demonstrated that the structurally normal X chromosome was late replicating (and hence presumably inactive) in 93% of the adult cells and 99% of the 9-day embryo cells, with the X¹⁶ chromosome late replicating in the remaining cells. We conclude from these results that in T16H/+ females either there is preferential inactivation of the normal X chromosome or that, if inactivation is random, cell selection takes place before 9 days of development. Two 9-day female embryos with an unbalanced karyotype were also studied; both had two late-replicating chromosomes in most of their cells, one being the chromosome 16^X, the other a normal X chromosome. These results, together with the presence of a late-replicating X¹⁶ chromosome in T16H/+ adult and fetal mice, support the concept that more than one inactivation center is present on the X chromosome of the mouse because the X¹⁶ and the 16^x chromosomes can be late replicating.     

No mutagenic or recombinogenic effects of mobile phone fields at 900 MHz detected in the yeast Saccharomyces cerevisiae

Both actively growing and resting cells of the yeast Saccharomyces cerevisiae were exposed to 900-MHz fields that closely matched the Global System for Mobile Communication (GSM) pulsed modulation format signals for mobile phones at specific absorption rates (SAR) of 0.13 and 1.3 W/kg. Two identical anechoic test chambers were constructed to perform concurrent control and test experiments under well-controlled exposure conditions. Using specific test strains, we examined the genotoxic potential of mobile phone fields, alone and in combination, with a known genotoxic compound, the alkylating agent methyl methansulfonate. Mutation rates were monitored by two test systems, a widely used gene-specific forward mutation assay at CAN1 and a wide-range assay measuring the induction of respiration-deficient (petite) clones that have lost their mitochondrial function. In addition, two further assays measured the recombinogenic effect of mobile phone fields to detect possible effects on genomic stability: First, an intrachromosomal, deletion-formation assay previously developed for genotoxic screening; and second, an intragenic recombination assay in the ADE2 gene. Fluctuation tests failed to detect any significant effect of mobile phone fields on forward mutation rates at CAN1, on the frequency of petite formation, on rates of intrachromosomal deletion formation, or on rates of intragenic recombination in the absence or presence of the genotoxic agent methyl methansulfonate.     

Sry induces cell proliferation in the mouse gonad

Sry is the only gene on the Y chromosome that is required for testis formation in mammals. One of the earliest morphological changes that occurs as a result of Sry expression is a size increase of the rudimentary XY gonad relative to the XX gonad. Using 5'-bromo-2'-deoxyuridine (BrdU) incorporation to label dividing cells, we found that the size increase corresponds with a dramatic increase in somatic cell proliferation in XY gonads, which is not detected in XX gonads. This male-specific proliferation was observed initially in the cells of the coelomic epithelium and occurred in two distinct stages. During the first stage, proliferation in the XY gonad was observed largely in SF1-positive cells and contributed to the Sertoli cell population. During the second stage, proliferation was observed in SF1-negative cells at and below the coelomic epithelium and did not give rise to Sertoli cells. Both stages of proliferation were dependent on Sry and independent of any other genetic differences between male and female gonads, such as X chromosome dosage or other genes on the Y chromosome. The increase in cell proliferation began less than 24 hours after the onset of Sry expression, before the establishment of male-specific gene expression patterns, and before the appearance of any other known male-specific morphological changes in the XY gonad. Therefore, an increase in cell proliferation in the male coelomic epithelium is the earliest identified effect of Sry expression.     

Effect of different doses of prostaglandin E2 on intrauterine pressure and uterine motility during diestrus in experimental cows

Studies in human medicine proved the important role of prostaglandin E2, which stimulates uterine contractions in vivo and in vitro and has been extensively used to ripen the cervix around labor. We wanted to demonstrate that increasing the dosage of prostaglandin E2 (1.25 mg, 2.5 mg, 5 mg and 10 mg) provokes an increase in intrauterine pressure and uterine motility in cattle. Five healthy, lactating dairy cows were used as experimental animals for this study. Intrauterine pressure was recorded during the diestrus phase (1 recording per cow and diestrus phase) by means of a transcervically placed intraluminal pressure microtransducer. Physiologic uterine motility was recorded for 30 min, then placebo or one of the prostaglandin E2- dosages was administered through an indwelling catheter in the jugular vein, followed by a 2-h recording period (eight 15-min periods). Area under the curve (AUC), mean amplitude, frequency of pressure waves and intrauterine pressure were analyzed. Furthermore, we recorded protocols for monitoring heart and respiratory rates and side effects at 9 given examination times. Significant differences were found for the AUC, the mean amplitude and the intrauterine pressure (P < or = 0.05), whereas the number of pressure waves per 15 min did not differ significantly among treatments. Peak values for AUC, mean amplitude and intrauterine pressure were found during the first 15 min after administration of 10 mg of prostaglandin E2. Dose-effect curves showed that the 2.5 mg dosage provided the optimal ratio between myometrial stimulation and undesirable side-effects.     

<Emphasis Type="Italic">TRAF1/C5</Emphasis>polymorphism is not associated with increased mortality in rheumatoid arthritis: two large longitudinal studies

Introduction  

Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients.     

Mesenchymal stem cells in autoimmune diseases: hype or hope?

Intervention with mesenchymal stem cells (MSCs) represents a promising therapeutic tool in treatment-refractory autoimmune diseases. A new report by Schurgers and colleagues in a previous issue of Arthritis Research & Therapy sheds novel mechanistic insight into the pathways employed by MSCs to suppress T-cell proliferation in vitro, but, at the same time, indicates that MSCs do not influence T-cell reactivity and the disease course in an in vivo arthritis model. Such discrepancies between the in vitro and in vivo effects of potent cellular immune modulators should spark further research and should be interpreted as a sign of caution for the in vitro design of MSC-derived interventions in the setting of human autoimmune diseases.