Variations in erythropoiesis throughout a lifetime. Studies in a high-leukaemic mouse strain, the AKR/O strain, and a non-leukaemic strain, the WLO strain

We have studied the development of some haematological variables: erythropoiesis stimulating factor(s) (ESF), investigated with an in vitro cell culture assay; and the content of bone marrow and spleen erythroid colony forming unit(s) (CFU-E) and erythroid burst forming unit(s) (BFU-E) throughout the lifetime of 2 different mouse strains: the high-leukaemic, retrovirus infected AKR/O strain, and the non-leukaemic WLO strain. During the recovery phase of the postnatal anaemia, a peak in plasma ESF occurs in both strains. In young adult mice of both strains another peak in plasma ESF occurs at 70-110 days of age, associated with an increased number of bone marrow CFU-E, in a period when packed cell volume (PCV) remains stable. As the animals grow older PCV decreases, whereas plasma ESF and bone marrow CFU-E concentration increase. These results, together with in vitro dose-response studies, suggest reduced sensitivity to erythropoietin (Epo) of the ageing erythron. Throughout, the AKR/O strain has higher levels of plasma ESF and bone marrow CFU-E concentrations than the WLO strain, indicating both a reduced Epo responsiveness and some degree of ineffective erythropoiesis in the AKR/O strain. At all ages the AKR/O strain has a high concentration of Epo independent bone marrow CFU-E, possibly caused by the virus infection of precursor cells.     

Development of a highly fecund inbred strain of mice

A highly fecund inbred mouse line has been established from the Quackenbush Swiss (QS) outbred strain by full-sib inbreeding combined with selection for high number of pups born alive (NBA) and low interlitter interval (ILI). After more than 50 generations of inbreeding and selection, this line, named QSi5, has an NBA of 13.4 and an ILI of 29 days, averaged over the first four parities, and a total productivity of 50.7 NBA. With its exceptional reproductive performance, this line will be very useful in the creation of resources (including advanced intercross lines) for analysis of quantitative trait loci for a wide range of traits, and for the cost-effective creation of congenic lines.     

A polydactylous strain of mice

Summary A highly inbred strain ofMus musculus is described in which 12% of the males and 18% of the females are polydactylous. This polydactyly is the only abnormality occurring in these mice. In most cases only the first digit (big toe) of the right hind foot is more or less duplicated, but the left foot and other toes may also be affected. Abnormal fathers transmit the peculiarity more often to their daughters than to their sons. This fact cannot be explained on a genetic basis, since for various reasons genetic differences between these mice cannot be assumed to exist. In general, polydactylous mice have an excess number of motor neurons innervating the foot in the spinal cord on the abnormal side. This may be the cause for polydactyly as is known to be inAmphibia.     

Infertility in mice infected genitally with a human strain of Chlamydia trachomatis

Progesterone-treated C3H and TO mice were inoculated genitally with a human C. trachomatis strain, serovar E, designated N.I. 1 or with 2SP control medium. Of the C3H mice serving as controls 93% had litters by the end of a 6-month period compared to 31% of mice infected with chlamydiae. This infertility could not be explained by tubal occlusion, since the oviducts appeared normal at autopsy. Some of the mice were induced to superovulate. Eggs were never recovered from the oviducts on the inoculated sides of infertile mice although they were sometimes found in the lumen of the uninoculated oviducts. In contrast, eggs were recovered routinely from both oviducts of control mice. In addition, eggs and/or their accompanying cumulus cells could be seen in the periovarial space of mice inoculated with chlamydiae, indicating a failure of the transportation of eggs to the oviduct. This could explain the high incidence of ectopic pregnancies in women after chlamydial infection. No adverse effect on fertility was seen in TO mice inoculated genitally with strain N.I.1. Of the mice given 2SP medium, 73% had litters, but 87% of the mice inoculated with chlamydiae were also fertile. There was, however, a significantly greater variation in the birth weights of mice born to infected TO mothers than those born to control mice. This difference in the susceptibility of mouse strains suggests that a genetic predisposition should also be considered for man.     

Syngeneic mixed lymphocyte reaction in mice: strain distribution, kinetics, participating cells, and absence in NZB mice.

Co-culture of mouse spleen nonadherent (T-enriched cells with mitomycin C-treated unfractionated syngeneic spleen cells resulted in increased DNA synthesis in the responding T cells. The kinetics of this syngeneic mixed lymphocyte reaction (SMLR) showed that peak DNA synthesis occurred on day 5 of culture compared to day 4 for conventional mixed lymphocyte reaction (MLR). Anti-T cell antiserum plus complement treatment of the responding cell population abolished the reaction, and similar treatment of the stimulator population enhanced SMLR. These studies indicate that SMLR represents the response of T cells to non-T cells. Studies on the generation of cytotoxic T lymphocytes (CTL) in parallel cultures of T cells activated by syngeneic or allogeneic spleen cells showed no cytotoxicity of SMLR-activated cells for either PHA- or LPS-induced blasts but did show a good CTL response of allo-activated cells to both targets. Studies on the strain distribution of SMLR revealed that NZB mice manifested poor or no stimulation in SMLR whereas all other strains tested exhibited strong SMLR. This defect in NZB mice may be pathogenetically related to the autoimmune disease that develops in these mice.     

Genetic control of juvenile growth rate in mice: variation between a congenic strain and its background strain

Studies on the genetic regulation of growth are confounded by the multigenic basis of growth. There is a need to isolate simplified genetic systems for the study of growth. We compared two closely related mouse strains and their F1 hybrids with regard to birth and weaning weights. The strains we used were C57BL/6 (B6) and a congenic derivative of B6 (HW54) that contains a short segment of BALB/c chromosome 7 spanning the H-24 and Gpi-1 loci. Despite the genetic similarity of these strains, they differed significantly in both birth and weaning weights. At birth, B6 pups were on average as much as 6.6% heavier than were pups from HW54. By the time of weaning, this trend was reversed; HW54 pups were as much as 13.8% heavier than were B6 pups. (B6 x HW54)F1 hybrids were intermediate between the parental strains in birth weight but were identical to B6 animals at weaning. An analysis of the F2 generation suggested that postnatal growth differences between B6 and HW54 are probably dependent on the maternal genotype. These strain-specific growth rates result from polymorphism at a restricted portion of the genome and represent a highly simplified system for the study of the genetics of growth.