Abstract:The purpose of this study was to develop a strain of canine X-linked muscular dystrophy (CXMD), a model of Duchenne muscular dystrophy, in Japan. A female beagle was artificially inseminated with frozen-thawed spermatozoa derived from an affected golden retriever. Subsequently, two carrier female dogs (G1 carriers) and four normal male littermates were produced. Thereafter, the two G1 carriers were mated with beagle sires. As a result, each bitch whelped three times, and out of 54 pups, 17 affected male descendants, and 11 carrier female descendants (G2 carriers) were detected. One G2 carrier was then mated with a beagle sire and 15 pups in two whelpings were produced, including five affected males and four carrier females (G3 carriers). A total of 10 female beagles were artificially inseminated to evaluate the fertility of the frozen-thawed spermatozoa from the two affected dogs. The whelping rates of the two affected dogs were 4/5 and the litter sizes were 5.0 ± 1.41 and 6.0 ± 0.82, respectively. These results indicate that a canine X-linked muscular dystrophy colony has been established in Japan. We called them CXMD J .

Background: Cardiac mortality in Duchenne muscular dystrophy (DMD) has recently become important, because risk of respiratory failure has been reduced due to widespread use of the respirator. The cardiac involvement is characterized by distinctive electrocardiographic abnormalities or dilated cardiomyopathy, but the pathogenesis has remained obscure. In research on DMD, Golden retriever-based muscular dystrophy (GRMD) has attracted much attention as an animal model because it resembles DMD, but GRMD is very difficult to maintain because of their severe phenotypes. We therefore established a line of dogs with Beagle-based canine X-linked muscular dystrophy in Japan (CXMD J ) and examined the cardiac involvement.

In vitro fertilization and embryo transfer were performed for rederivation of four strains of mice harbouring mouse hepatitis virus (MHV) and/or Pasteurella pneumotropica (P. pneumotropica). Superovulated oocytes were fertilized by preincubated cauda epididymis sperm in vitro. Fertilized eggs at 2-cell stage were transferred into the oviducts of specific pathogen free (SPF) recipients. Microbial examination of sperm and/or oocyte donors verified the presence of P. pneumotropica and/or of antibodies to MHV in all strains, but neither in the recipients nor in the offspring antibodies to MHV could they be detected. The results indicate that an in vitro fertilization-embryo transfer (IVF-ET) system is an effective and simple alternative to cesarean operation in infected mice.

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1 The protein binding of disopyramide was measured in plasma obtained from nonpregnant women, pregnant women in the first, second, and third trimesters, matched pairs of mothers and neonates (cord plasma), and 1 month postpartum women (n = 6 or 8 of each). 2 Plasma samples spiked with 0.2-12.0 ug ml-l of the drug were ultrafiltered and the free fractions were measured with a fluorescent polarization immunoassay.3 The mean (± s.d.) percentages of free drug at a total concentration of 3.0 pug ml-' observed in the third trimester (46 ± 9%) and neonate (79 ± 5%) groups were greater (P < 0.05 or 0.01) than that in the non-pregnant group (34 + 7%). In contrast, the corresponding value observed in the postpartum group (23 ± 8%) was less (P < 0.05) than that in the non-pregnant group. In addition, there was a significant (P < 0.01) difference in the mean percentage of free drug at 3.0 ,ug ml-' in plasma from mothers (43 ± 9%) and neonates (79 ± 5%).4 A multiple regression analysis indicated that a,-acid glycoprotein (r = -0.88, P < 0.01), rather than albumin (r = -0.008), dominated the binding of disopyramide within the therapeutic range of drug concentration. An analysis of the binding parameters of disopyramide suggested that alterations in binding were attributable to changes in the capacity rather than the affinity of binding. 5 These data suggest that: 1) the antiarrhythmic effects of disopyramide at a given total (free + bound) therapeutic plasma concentration may be greater in women in the third trimester of pregnancy and in neonates, but may be reduced in postpartum women at 1 month, compared with non-pregnant women; 2) plasma a,-acid glycoprotein concentration may serve as a useful index to predict alterations in disopyramide binding; and 3) the mean foetal/maternal total plasma concentration ratio of disopyramide within the therapeutic total drug concentration of 2.0 to 5.0 jig ml-' in maternal plasma should be about 0.78.Keywords disopyramide protein binding pregnancy neonate postpartum ao-acid glycoprotein