A candidate model for Angelman syndrome in the mouse.

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are well-recognized examples of imprinting in humans. They occur most commonly with paternal and maternal 15q11-13 deletions, but also with maternal and paternal disomy. Both syndromes have also occurred more rarely in association with smaller deletions seemingly causing abnormal imprinting. A putative mouse model of PWS, occurring with maternal duplication (partial maternal disomy) for the homologous region, has been described in a previous paper but, although a second imprinting effect that could have provided a mouse model of AS was found, it appeared to be associated with a slightly different region of the chromosome. Here, we provide evidence that the same region is in fact involved and further demonstrate that animals with paternal duplication for the region exhibit characteristics of AS patients. A mouse model of AS is, therefore, strongly indicated.

Ubiquitous expression and imprinting of Snrpn in the mouse.

Snrpn is known to be abundantly expressed in rodent brain and heart, and in two separate studies with neonatal mouse brain it has been shown to be maternally imprinted, that is, the maternal allele is normally repressed. We now provide evidence on the expression profile and imprinting status of Snrpn throughout development. Using RT-PCR, we have established that Snrpn is further expressed at low levels in lung, liver, spleen, kidney, skeletal muscle, and gonads. Moreover, using mice with only maternal copies of Snrpn (maternal duplication for the chromosome region involved and parthenogenotes), we have shown that the gene is imprinted in all of these tissues and, generally, from the time the gene is first expressed at 7.5 days gestation. In contrast to the findings made with the imprinted genes, Igf2, Ins1, and Ins2, there is no evidence of tissue-specific imprinting in the embryo with Snrpn. Nor, as found with Igf2 and Igf2r, is there evidence of a window of biallelic expression between the germ line imprint and the time of gene repression. The absence of Snrpn expression in early embryos contrasts with the findings in ES cells.

Mice lacking Snrpn expression show normal regulation of neuronal alternative splicing events.

The SmN protein is closely related to the constitutively expressed RNA splicing protein SmB but is expressed only in brain and heart tissue. Mice which lack expression of SmN die shortly after birth suggesting a critical role for this protein possibly in the regulation of neuronal-specific alternative splicing events. We show here however that the neuronal-specific alternative splicing of the RNAs encoding several different classes of protein proceeds normally in mice lacking SmN expression. The potential role of SmN and the reasons for the lethal effect observed in non-expressing mice are discussed.

A candidate mouse model for Prader-Willi syndrome which shows an absence of Snrpn expression.

The best examples of imprinting in humans are provided by the Angelman and Prader-Willi syndromes (AS and PWS) which are associated with maternal and paternal 15q11-13 deletions, respectively, and also with paternal and maternal disomy 15. The region of the deletions has homology with a central part of mouse chromosome 7, incompletely tested for imprinting effects. Here, we report that maternal duplication for this region causes a murine imprinting effect which may correspond to PWS. Paternal duplication was not associated with any detectable effect that might correspond with AS. Gene expression studies established that Snrpn is not expressed in mice with the maternal duplication and suggest that the closely-linked Gabrb-3 locus is not subject to imprinting. Finally, an additional new imprinting effect is described.

Pulmonary artery catheterization: the right heart should not be left out--a case report.

Tricuspid valve stenosis in the setting of endocarditis is associated with a high morbidity. Diagnostic approaches incorporate a high clinical index of suspicion, echocardiographic evidence, and inferences about hemodynamic data derived from pulmonary artery catheterization. As demonstrated by the case presented herein, inadequate initial evaluation of right-sided pressures delayed the diagnosis and treatment of prosthetic tricuspid valve stenosis.

Basal, sham feed and pentagastrin stimulated gastric acid, pepsin and electrolytes after omeprazole 20 mg and 40 mg daily.

Gastric secretion was measured in nine patients with duodenal ulcer before, and after treatment for four weeks with omeprazole 20 mg or 40 mg daily. Basal acidity and acid output were affected variably by 20 mg, but inhibited totally by 40 mg daily. Sham feed stimulated acid output was reduced by 20 mg daily and completely inhibited by 40 mg daily. Maximal pentagastrin stimulated acid output was halved by 20 mg omeprazole daily and 84% inhibited by 40 mg daily. The reduction in acidity was always greater than the reduction of volume. Pepsin output after pentagastrin was little altered but with the reduced secretory volume pepsin concentrations were increased by both doses. The major cause of reduced aspirate acid output after omeprazole is decreased secretion of the primary acid component of the parietal cell by the proton pump H+K+ ATPase. Duodenogastric alkaline reflux is, however, markedly increased after omeprazole and is an additional factor in the resultant hypoacidity or even anacidity after this drug.

Transmission of human T-cell lymphotropic virus type III (HTLV-III) by artificial insemination by donor.

Four of eight recipients of artificial insemination (AI) with cryopreserved semen from a symptomless carrier of human T-cell lymphotropic virus type III (HTLV-III) were found to have antibody to the virus. One has generalised, persistent lymphadenopathy while the other three remain symptom free 3 years after insemination. Three subsequently became pregnant more than a year after contact with the infected semen; the children, who are now over 1 year of age, are in good health and do not have HTLV-III antibodies. These observations emphasise the need for a rigorous screening programme for potential AI donors; they also suggest that fresh semen should not be used in AI. The findings confirm the role of semen in heterosexual transmission of the virus and suggest that in women with HTLV-III antibodies pregnancy and subsequent breast-feeding does not necessarily lead to infection of the infant.