Genetical studies on the skeleton of the mouse XVIII. Three genes for syndactylism

Abstract

1. The recessive gene for syndactylism (sm) has reduced viability at birth, and soon after, but nearly normal viability and fertility later on. All four feet are regularly affeeted. Syndactylism involves primarily digits 3 and 4, while digit 2 is also not rarely involved. Fusions are usually osseous in the hindfeet, but often by soft tissues only in the forefeet. Phalanges only are involved, usually all three of them, while metacarpals and metatarsals are not affected. The naviculare and cuboideum tend to be fused. The fusions between phalanges are primary, those between tarsalia secondary. Anomalies in the distal half of the tail are present in manysm/sm mice. 2. The semi-dominant gene for Oligosyndactylism. (Os) is lethal in homozygous condition, but of normal viability and fertility in heterozygotes. All four feet are regularly affected. Syndactylism is usually confined to digits 2 and 3, but digit 4 is occasionally also involved. Soft-tissue fusions are more common on the forefeet, hard-tissue fusions on the hindfeet. Fusions seem, to start at the basal phalanx and thence spread first distally; after all phalanges are fused, the process spreads in a proximal direction involving metacarpals and metatarsals. Fusion may be so complete as to lead to a four-toed foot in which there is either a composite digit representing rays 2 and 3, or in which dgit 2 has completely disappeared; sometimes the material for digit 2 seems to be shifted. to wards digit 1 which may then be duplicated. There are always extensive fusions in carpus and tarsus; these include a primary fusion between cuboideum and cuneiforme 3, all others being secondary. Fusions between some phalanges are also primary, but the majority of these and between metacarpals and metatarsals are secondary; these include particularly fusions between the proximal ends of metacarpalia and metatarsalia 4 and 5 which are secondary to the reductions in carpus and tarsus respectively. 3. The recessive gene for shaker with syndactylism (sy) is semi-lethal, in that many animals die soon after birth, and none reach sexual maturity. Most hindfeet are affected, but normal overlapping in the forefeet is common. Anomalies involve either digits 2 and 3, or digits 3 and 4, or all three of them; the relative frequency of these fusions is partly controlled by the genetic background. As insm/sm, fusions are confined to the phalanges and apparently all primary; metacarpals and metatarsals are not affected, but there are fairly extensive secondary fusions in carpus and tarsus. In addition to the anomalies on the feet, there is a general involvement of the skeleton; the long bones have thin shafts, but epiphyses of nearly normal size; there are also shape anomalies of seapula and of the sacral vertebrae. These anomalies are preformed in cartilage and can be seen in the newborn animal. Whether they are due to a disturbance of chondrification or of cartilage growth is unknown. 4. Fusions between certain carpalia and/or tarsalia have been encountered both in the inbred strains A/Gr, CBA/G-r, C57BL/Gr and BALB/c and in heterogeneous stocks of mice. Thus BALB/c regularly has a fusion between multangulum minus and centrale, C57 BL has the same fusion associated with fusion between naviculare and cuneiforme 3, while other strains either lack these fusions completely or have small percentages. These fusions, or their absence, are thus under genetical control.