We have developed a method to produce live somatic clones in the rabbit, one of the mammalian species considered up to now as difficult to clone. To do so, we have modified current cloning protocols proven successful in other species by taking into account both the rapid kinetics of the cell cycle of rabbit embryos and the narrow window of time for their implantation after transfer into foster recipients. Although our method still has a low level of efficiency, it has produced several clones now proven to be fertile. Our work indicates that cloning can probably be carried out successfully in any mammalian species by taking into account physiological features of their oocytes and embryos. Our results will contribute to extending the use of rabbit models for biomedical research.

Objective-Plasma phospholipid transfer protein (PLTP) is involved in intravascular lipoprotein metabolism. PLTP is known to act through 2 main mechanisms: by remodeling high-density lipoproteins (HDL) and by increasing apolipoprotein (apo) B-containing lipoproteins. The aim of this study was to generate a new model of human PLTP transgenic (HuPLTPTg) rabbit and to determine whether PLTP expression modulates atherosclerosis in this species that, unlike humans and mice, displays naturally very low PLTP activity. Methods and Results-In HuPLTPTg rabbits, the human PLTP cDNA was placed under the control of the human eF1-␣ gene promoter, resulting in a widespread tissue expression pattern and in increased plasma PLTP. The HuPLTPTg rabbits showed a significant increase in the cholesterol content of the plasma apoB-containing lipoprotein fractions, with a more severe trait when animals were fed a cholesterol-rich diet. In contrast, HDL cholesterol level was not modified in HuPLTPTg rabbits. Formation of aortic fatty streaks was increased in hypercholesterolemic HuPLTPTg animals as compared with nontransgenic littermates. Key Words: atherosclerosis Ⅲ lipoproteins Ⅲ metabolism Ⅲ transgenic models H uman plasma contains 2 distinct lipid transfer proteins (cholesteryl ester transfer protein [CETP] and phospholipid transfer protein [PLTP]) that promote the rapid exchange of lipid species between circulating lipoproteins, as well as between circulating lipoproteins and cells. 1 Although most reported data agree that the putative implication of CETP in lipoprotein metabolism and atherosclerotic process mostly concerns the net transfer of cholesteryl esters from antiatherogenic high-density lipoproteins (HDL) to potentially atherogenic apolipoprotein (apo) B-containing lipoproteins, 1 the precise function of PLTP and its consequences in terms of atherogenesis remain a matter of debate. PLTP was identified initially for its ability to promote the transfer of phospholipids from triglyceride-rich lipoproteins to HDL in the postprandial phase. 2 Subsequent studies reported that PLTP is also a key player in the HDL conversion process, leading to the emergence of large and small HDL products. 3,4 Recently, PLTP in human plasma was shown to reside mainly on lipid-poor complexes in association with proteins linked to immunity and inflammation, suggesting that the biological function of PLTP is rather complex in nature. 5 In support of this view, PLTP expression in the mouse was found to increase the production of apoB-containing lipoproteins by the liver 6 and intestine, 7 to decrease very low density lipoprotein (VLDL) catabolism, 8 to reduce the antioxidant protection of atherogenic lipoproteins, 9,10 to trigger inflammation, 11 and to promote the association of lipopolysaccharides with circulating lipoproteins. 12 All these properties have long been shown to influence the atherosclerotic process, whether acting individually or in a combined manner. Conclusion-HumanHigh plasma PLTP concentrations were earlier reported in diabetic...

The heterozygous prolactin (PRL) receptor (PRLR +/-) mouse fails to develop a fully functional mammary gland at the end of the first pregnancy and shows markedly impaired lobuloalveolar development and milk secretion in young females. The PRLR is expressed ubiquitously, with various proportions of long and short isoforms in different tissues. Conflicting data have appeared on the putative role of the receptor short forms, with both agonist and antagonistic actions proposed. To assess whether the mouse PR-1 short isoform of the PRLR is potentially able to transduce a signal, we overexpressed it in heterozygous mice and investigated its effect on the rescue of mammary development. PRLR+/- mice were not able to develop a functional mammary gland, but restoration of mammary alveolar development and an increase in the expressions of casein and whey acidic protein genes were observed in transgenic PRLR+/- mice expressing the short form of the PRLR, leading to a complete rescue of mammary gland development and function in young females. These results demonstrate that PR-1, the short form of the PRLR, can improve mammary development in PRLR+/- mice, which compensates for the haploinsufficiency of the receptor long form; this effect is probably caused by accelerated proliferation and an activation of the PRLR signaling cascade, resulting in activation of target genes involved in mammary development and milk synthesis.

Human apolipoprotein A-I (apo A-I) transgenic rabbits were created by use of an 11-kb genomic human apo A-I construct containing a liver-specific promoter. Five independent transgenic lines were obtained in which human apo A-I gene had integrated and was expressed. Plasma levels of human apo A-I ranged from 8 to 100 mg/dL for the founder and up to 175 mg/dL for the progeny. Rabbit apo A-I levels were substantially decreased in the transgenic rabbits. HDL cholesterol (HDL-C) levels were higher in two of the five transgenic rabbit lines than in controls (line 20 versus nontransgenic littermate, HDL-C = 80 +/- 7 versus 37 +/- 6 mg/dL; line 8 versus nontransgenic littermate, HDL-C = 54 +/- 16 versus 35 +/- 6 mg/dL). This resulted in less atherogenic lipoprotein profiles, with very low (VLDL + LDL-C)/HDL-C ratios. HDL size and protein and lipid compositions were similar between transgenic and littermate nontransgenic rabbits. However, a large amount of pre-beta apo A-I-containing lipoproteins was observed in the plasma of the highest human apo A-I expressor. Cell cholesterol efflux was evaluated with the incubation of whole serum from transgenic and control rabbits. Cell cholesterol efflux was highly correlated with HDL cholesterol, with apo A-I, and with the presence of pre-beta apo A-I-containing lipoproteins. These rabbits will be an extremely useful model for the evaluation of the effect of increased hepatic apo A-I expression on atherosclerosis.