Hemorrhage, impaired hematopoiesis, and lethality in mouse embryos carrying a targeted disruption of the Fli1 transcription factor.

The Ets family of transcription factors have been suggested to function as key regulators of hematopoeisis. Here we describe aberrant hematopoeisis and hemorrhaging in mouse embryos homozygous for a targeted disruption in the Ets family member, Fli1. Mutant embryos are found to hemorrhage from the dorsal aorta to the lumen of the neural tube and ventricles of the brain (hematorrhachis) on embryonic day 11.0 (E11.0) and are dead by E12.5. Histological examinations and in situ hybridization reveal disorganization of columnar epithelium and the presence of hematomas within the neuroepithelium and disruption of the basement membrane lying between this and mesenchymal tissues, both of which express Fli1 at the time of hemorrhaging. Livers from mutant embryos contain few pronormoblasts and basophilic normoblasts and have drastically reduced numbers of colony forming cells. These defects occur with complete penetrance of phenotype regardless of the genetic background (inbred B6, hybrid 129/B6, or outbred CD1) or the targeted embryonic stem cell line used for the generation of knockout lines. Taken together, these results provide in vivo evidence for the role of Fli1 in the regulation of hematopoiesis and hemostasis.

Phenotypic variation in seasonal adjustments of testis size, body weight, and food intake in deer mice: role of pineal function and ambient temperature.

We investigated pineal function as well as reproductive and energetic characteristics in male deer mice (Peromyscus maniculatus) that differentially respond to short photoperiod with full, partial or no gonadal regression. In mice at both high (23 degrees C) and low temperature (1 degree C), these phenotypic differences in reproductive responses to short days were not reflected by differences in urinary excretion of 6-sulphatoxy-melatonin, the main metabolite of pineal melatonin. Neither duration nor amplitude or phase-angle of nocturnal peaks in 6-sulphatoxymelatonin significantly differed between reproductive phenotypes at either temperature. Differences in testis size were, however, associated with different energy requirements. In gonadally regressed males only, food intake and body weight were significantly (P < 0.01) reduced by up to 29% and 13% respectively. Chronic cold exposure (5 degrees C) had no effect on the proportion of males undergoing testicular regression under short days, but caused a general elevation in body weights among all mice (P < 0.05). Phenotypic differences in body weight and food intake were maintained in the cold. Together, these results suggest that within-population variation of reproductive responses in male deer mice is based on post-pineal differences in the regulation of gonadal function, and that phenotypic characteristics in reproductive and energetic responses to short days are largely unaffected by ambient temperature.