The autosomal recessive gene for brachypodism (bp) in the mouse affects the appendicular, but not the axial skeleton. Manus and pes are more severely affected than the rest of the limbs; the girdles are normal. In digits 2–5, the basal and middle phalanges of the normal are replaced by a short and thin element which never ossifies properly; by contrast, the terminal phalanges are normal or nearly so. Up to the 13-day stage, the limbs of brachypods are externally quite normal, but anomalies of the digital blastemata are detectable in the 12-day embryo already, i.e. before the onset of chondrification. In the 14-day embryo, the overall length of metapod + phalanges is still nearly normal; but the basal and middle phalanges of the normal are represented by a single thin element which is absolutely longer whereas the metacarpale (metatarsale) is correspondingly reduced in length and calibre. This situation is subsequently reversed by heterogonic growth as the phalangeal element of brachypods grows very little. The normality of the terminal phalanges is largely due to the fact that, in the mouse, much of the terminal phalanx is formed directly from membrane and not by replacement of its cartilaginous ‘model’ on which it sits like a thimble. Brachypodism is thus due to an abnormality of the limb blastemata which precedes chondrification, but whose nature is unknown. Generally, muscular and tendinous anomalies parallel those of the skeleton.
Genetic studies of a new mutant strain showing shivering in the mouse
