Only mammals have relinquished parthenogenesis, a means of producing descendants solely from maternal germ cells. Mouse parthenogenetic embryos die by day 10 of gestation. Bi-parental reproduction is necessary because of parent-specific epigenetic modification of the genome during gametogenesis. This leads to unequal expression of imprinted genes from the maternal and paternal alleles. However, there is no direct evidence that genomic imprinting is the only barrier to parthenogenetic development. Here we show the development of a viable parthenogenetic mouse individual from a reconstructed oocyte containing two haploid sets of maternal genome, derived from non-growing and fully grown oocytes. This development was made possible by the appropriate expression of the Igf2 and H19 genes with other imprinted genes, using mutant mice with a 13-kilobase deletion in the H19 gene as non-growing oocytes donors. This full-term development is associated with a marked reduction in aberrantly expressed genes. The parthenote developed to adulthood with the ability to reproduce offspring. These results suggest that paternal imprinting prevents parthenogenesis, ensuring that the paternal contribution is obligatory for the descendant.

Although MIF plays multifunctional roles in a broad spectrum of pathophysiological states, little has been done to investigate the role of this protein in association with tumor growth. The current results suggest the possibility that MIF induces tumor cell growth in concert with other growth factors, which encouraged us to investigate a novel approach for tumor therapy using an anti-MIF antibody and an MIF anti-sense plasmid transfection technique.

We evaluated the effects of aging and hypertension on endothelium-dependent relaxation of rat common carotid arteries using 14-week-old (young) and 11-month-old (old) Wistar-Kyoto rats (WKY) and age-matched spontaneously hypertensive rats (SHR). Isometric tension of common carotid artery ring segments was measured. With a resting tension of 2.0 g determined from the baseline tension-contraction curves, precontraction was induced by 10" and hypertension 13 -16 on vascular reactivity in general have been extensively studied. In addition, there are several reports examining the influence of aging or hypertension on endothelium-dependent vasodilatations. 17 -21 In these studies, ACh-induced relaxation of rat mesenteric artery was unaffected by age, 17 whereas hypertension impaired endothelium-dependent relaxation in experimental animals. 18 -21 There are at present, however, noFrom the Department of Neurosurgery, University of Virginia School of Medicine, Charlottesville, Virginia.Address for correspondence: Neal F. Kassell, MD, Department of Neurosurgery, Box 212, Medical Center, University of Virginia, Charlottesville, VA 22908.Received June 30, 1987; accepted February 3, 1988. reports of the effects of aging or hypertension on the endothelium-dependent relaxations of cephalic arteries. This is surprising considering the major effects that aging and hypertension are thought to exert on the cerebral circulation.Recently Freiman et al 22 demonstrated that atherosclerosis impairs endothelium-dependent vascular relaxation to ACh and thrombin in monkeys. The common carotid artery, which is often affected by disorders such as atherosclerosis, has a great influence on cerebral circulation. Therefore, it seems pertinent to investigate the effects of aging and hypertension on the endothelium-dependent vascular relaxation in a cephalic artery such as the common carotid artery. Our experiments were designed to demonstrate these effects using young and old Wistar-Kyoto rats (WKY) and young and old spontaneously hypertensive rats (SHR).

The cluster of imprinted genes located in the Dlk1-Dio3 domain spanning 1 Mb plays an essential role in controlling pre- and postnatal growth and differentiation in mice and humans. The failure of parent-of-origin-dependent gene expression in this domain results in grave disorders, leading to death in some cases. However, little is known about the role of maternally expressed non-coding RNAs (ncRNAs) including many miRNAs and snoRNAs in this domain. In order to further understand the role of these ncRNAs, we created Gtl2-mutant mice harboring a 10 kb deletion in exons 1-5. The mutant mice exhibited a very unique inheritance mode: when the deletion was inherited from the mother (Mat-KO), the pups were born with normal phenotypes; however, all of them died within 4 weeks after birth, probably due to severely hypoplastic pulmonary alveoli and hepatocellular necrosis. Mice carrying the paternal deletion (Pat-KO) showed severe growth retardation and perinatal lethality. Interestingly, the homozygous mutants (Homo-KO) survived and developed into fertile adults. Our results show that these phenotypes occur due to altered expression of the Dlk1-Dio3 cluster genes including miRNAs and snoRNAs via the cis and trans effects.

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