Esophageal basement membranes (arrows) are thick and disorganized in collagen mutant mice (right).

No collagen XIX is hard to swallow, at least for mice lacking this extremely rare matrix protein. On page 591, Sumiyoshi et al. reveal that loss of collagen XIX disrupts muscle function in the murine esophagus.

Collagen is the most abundant protein in the body, but there are at least 27 different types, some more common than others. Although collagen XIX is scarce, the authors find it is necessary for survival into adulthood.

Mice that made no collagen XIX died within a few days after birth. These mice had an enlarged esophagus and signs of malnutrition. The distended esophagus was a result of impaired muscle function in the lower esophagus that prevented the relaxation needed for swallowing. The same muscle problem was seen in mice that made a less flexible mutant collagen XIX version, but these mice survived to adulthood.

Collagen XIX is associated with and signals to muscle cells from the basement membrane, which instructs tissue differentiation. In the mouse esophagus, smooth muscle cells change gradually into skeletal muscle beginning before birth. Loss of collagen XIX prevented the expression of the transcription factors needed for this transition, so smooth muscle was retained in the adult esophagus.

This defect does not seem to be due to changes in the structure of the extracellular matrix, as the less flexible collagen XIX mutant was still able to direct muscle transition. Collagen XIX may be required to organize the matrix such that growth factors needed for muscle development are properly presented to the cells. Alternatively, it may signal to cells directly or by binding to other matrix factors, such as proteoglycans. ▪