Delayed hematopoietic development in osteopetrotic (op/op) mice.

Changes in structure, cellularity, hematopoietic progenitor cell and macrophage content, and osteoclast activity were investigated in the hematopoietic organs of the colony-stimulating factor 1(CSF-1)-less osteopetrotic (op/op) mouse. The data indicated that op/op mice undergo an age-related hematopoietic recovery and resolution of osteopetrosis, suggesting that the hematopoietic system has the capacity to use alternative mechanisms to compensate for the absence of an important multifunctional growth factor, CSF-1. In young animals, op/op femurs were heavily infiltrated with bone, and marrow cellularity was significantly reduced. After 6 wk of age, there was an increase in the marrow space available for hematopoiesis. The femoral cavity of op/op mice progressively enlarged, and by 22 wk of age its appearance and marrow cellularity was comparable to that of controls. The percentage of op/op mononuclear phagocytes, defined by F4/80 antigen expression, progressively increased to normal levels by 35 wk of age. There was no difference in the incidence of both primitive and mononuclear phagocyte-committed, CSF-1-responsive progenitor cells in op/op marrow, but their femoral content was significantly reduced in young mice. During the period of reduced hematopoiesis in the marrow of young op/op mice, splenic hematopoietic activity was elevated. This mutant mouse represents a system for the study of the CSF-1-independent regulatory mechanisms involved in hematopoietic regulation.

Diversity of putative Tn5253-like elements in Streptococcus pneumoniae.

Pneumococcal resistance to tetracycline, chloramphenicol, erythromycin and clindamycin is often attributed to carriage of conjugative transposons of the Tn916 family. The less well studied conjugative transposon Tn5253 is a composite transposon consisting of a Tn916-like element inserted within the unrelated Tn5252 element, which has also been associated with chloramphenicol and tetracycline resistance. Here, carriage of the Tn5252 integrase (int(5252)), Tn5252-encoded umuC and umuD homologues and Tn916 integrase (int(916)) was examined among 55 clinical isolates of Streptococcus pneumoniae resistant to one or more of the above mentioned antibiotics. Tn5253-associated genes were common among the antibiotic-resistant S. pneumoniae examined, including members of international clones, although the spectrum of genes and resistances carried was diverse. Analysis of five isolates demonstrated insertion of a Tn5253-related element at the same chromosomal locus but sequence and restriction site diversity. This study shows for the first time a high degree of variability of Tn5253-related elements within clinical isolates of pneumococci. The fact that these elements are prevalent among internationally recognised pandemic clones warrants a more intensive investigation.