Background and gender effects on survival in the TgN(SOD1-G93A)1Gur mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder. While most cases of ALS are sporadic, 10-15% are familial, and of these 15-20% possess a mutation in the gene that codes for the enzyme Cu/Zn superoxide dismutase (SOD1). In families of ALS patients with specific SOD1 mutations, affected members demonstrate significant heterogeneity of disease and a large variation in age of onset and severity, suggesting that there are genetic modifiers of disease expression. Transgenic mice expressing mutant forms of SOD1 demonstrate symptoms similar to those seen in patients with ALS. We have observed in our colony of G93A SOD1 transgenic mice a milder phenotype in mice in a C57BL/6J background than the C57BL/6JxSJL/J hybrid background used by Jackson Laboratories to maintain their colony. To investigate the effect of genetic background on phenotype, we have constructed congenic lines on two genetic backgrounds, C57BL/6J (B6) and SJL/J (SJL). We report the influence of background and gender on the survival of these congenic lines compared to the hybrid C57BL/6JxSJL/J background. The mean survival of G93A SOD1 mice in the hybrid B6/SJL background was 130 days, with females surviving significantly longer than males. When compared to the hybrid B6/SJL background, the survival of mice in the SJL background significantly decreased, and the gender difference in survival was maintained. On the other hand, mean survival in the B6 background significantly increased, and in contrast to the B6/SJL and SJL backgrounds, there was no difference in survival between males and females. Transgene copy numbers were verified in all animals to ensure that any phenotypic differences observed were not due to alterations in copy number. This is the first report of a shortened lifespan when the G93A SOD1 transgene is placed on the SJL/J background and an increased survival with the loss of gender influences when the transgene is placed on the C57BL/6J background.

[The complex etiology of epidemic diseases in calves on large-capacity farms and their clinical and epizootic characteristics]. / Komplexní etiologie hromadných onemocnení telat na velkokapacitních farmách a jejich klinická a epizootologická charakteristika.

It is not easy to exactly diagnose the etiology of the mass infections of new-born calves on large farms where considerable losses are suffered. On the basis of the complex epizootological, clinical and laboratory examination in four large calf-rearing facilities, rotaviruses, coronaviruses, the infectious bovine rhinotracheitis (IBR) virus and the bovine viral diarrhoea (BVD) virus, and in some cases also the enteropathogenic E. coli, were found to be etiologically involved in the mass rise of diarrhoea, complicated by respiratory symptoms already during the first days after birth. The clinical picture of the disease, therapeutically difficult and reminding of "pneumoenteritis", has often been observed in stocks where, in addition to rotaviruses and coronaviruses in the faeces, the IBR or BVD viruses (sometimes both at the same time) were detected and identified in the respiratory and enteral tract. The serological examination of a higher number of animals in the stocks of calves under study confirmed the considerable rate of spreading of all the four viruses in the cattle population and, at the same time, demonstrated the very unfavourable immunological profile of the herds. The high percentage of animals low in antibody titres and the serologically negative animals constitute the infection-sensitive part of population in the affected herds. With the high culling rate and with the open herd turnover it is impossible to reach the required immunity through natural disinfection. Loss-free rearing of healthy calves will be achieved on the basis of a well-oriented vaccination programme with a good combination of inoculants.

Morphogenesis of the spinal canal, normal and stenotic.

The closest formative developmental dependence of the axial skeleton upon the morphogenesis of the intraspinal nervous structures is reflected in the roentgen features of the individual vertebrae as well as of the vertebral column in its entirety. The vertebroneural developmental events are characterized by a steady relative decrease in size of the nervous structures (the first to be laid down and huge in the embryonic period) under a corresponding increase in size of the skeletogenic tissues. There exists experimental evidence that the maintenance of the necessary developmental balance between the two tissues, the bony and the skeletogenic, is a function of the nervous substance. The tight spinal canal appears to result from a failure of the latter neural function leading to overgrowth of the bony structures, viz., to massive vertebrae and laminae encroaching upon the neural contents. Morphogenesis of the normal and tight lumbar spinal canal is discussed with special reference to the developmental interrelations between the cauda equina complex and the lumbar vertebrae.