Doublefoot: a new mouse mutant affecting development of limbs and head.

The mutant doublefoot, Dbf, of the mouse arose spontaneously, and was shown to be inherited as an autosomal dominant, mapping 9-13 cM proximal to leaden, In, on chromosome 1 and showing no recombination with the microsatellite markers D1Mit24 and D1Mit77. In heterozygotes the phenotype includes many extra toes on all four feet, and the tibia and fibula may be reduced and bowed. The head is shortened and broad and the eyes are held half-closed, and some animals develop hydrocephalus. The tail is kinked and abnormally thick, and the soles of the feet are swollen. Growth is retarded, viability is reduced, and reproduction is impaired in both sexes. Only about 30% of males are normally fertile, and testis weights and sperm counts may be reduced, although this appears not to be the main cause of poor fertility. In females vaginal opening is delayed and oestrous cycles are irregular, although the animals appear to respond to gonadotrophic hormones. Crosses of Dbf/+ x Dbf/+ are very poorly fertile. Prenatally, Dbf/+ heterozygotes can first be recognized at 11 1/2 days gestation by abnormally broad fore limb buds. Putative Dbf/Dbf homozygotes at 12 1/2 days have similar limbs defects and also split face, due to failure of the maxillae to fuse in the midline. Some homozygotes and a few putative heterozygotes have cranioschisis. At 13 1/2 days, the heads of homozygotes tend to bulge in the frontal region and a bleb of clear fluid is visible medially. At 14 1/2 days Dbf/Dbf fetuses may have oedema and some are dead. From 15 1/2 days onwards no live Dbf/Dbf fetuses have been found. The gene maps close to the locus of Pax3, but crossovers between Dbf and Pax3 have been found, ruling out the possibility that a gain-of-function mutation in Pax3 might be involved.

The response of spontaneous and transplantable murine tumors to vasoactive agents measured by 31P magnetic resonance spectroscopy.

31P magnetic resonance spectroscopy has been used to compare the effects of the vasoactive agents hydralazine and flunarizine on the oxygenation of the transplantable tumors, SCCVII/Ha and 16C, and a range of spontaneous mammary tumors arising in the breeding stock in the Genetics Division at the Radiobiology Unit. The vasodilator hydralazine, previously shown to increase the radiobiological hypoxic fraction of transplantable murine tumors, increased inorganic phosphate to total phosphate (Pi/total) in SCCVII/Ha and 16C tumors. However, only two spontaneous tumors responded to this agent (2/12). The calcium antagonist flunarizine, which sensitizes the SCCVII tumor to X rays, consistent with a reduction in hypoxic fraction, reduced Pi/total in this and the 16C tumor. Further, most spontaneous tumors tested (8/10) responded to this agent, as measured by a reduction in Pi/total. These results point to fundamental differences between transplantable and spontaneously arising tumors in mice in their response to vasoactive agents.

Tracheal stenosis in infants and young children.

Eight cases of intra-thoracic tracheal stenosis presenting to the ENT department at the Hospital for Sick Children, Great Ormond Street, over the past 10 years are reported. The varied aetiology and presentation of these cases is discussed and the frequency of associated cardio-pulmonary anomalies emphasized. Difficulties in diagnosis and investigation are outlined, in addition to an overview of current management. While the overall outlook for many of these children remains poor there is reason to believe that a balance of conservative management and surgical reconstruction in selected cases will result in improved survival figures.