Tight-skin, a new mutation of the mouse causing excessive growth of connective tissue and skeleton

A new dominant mutation, tight-skin (Tsk), is located on Chromosome 2, two recombination units distal to pallid (pa). Heterozygotes (Tsk/+) have tight skins with marked hyperplasia of the subcutaneous loose connective tissues, increased growth of cartilage and bone, and small tendons with hyperplasia of the tendon sheaths. In the loose connective tissue there are large accumulations of microfibrils in the intercellular space. In spite of the increased skeletal size, body weight is not increased. Increase in size of the thoracic skeleton is especially pronounced and leads to pathologic distentsion of the hollow thoracic viscera. Concentration of growth hormone in the pituitary and plasma is normal. Homozygotes (Tsk/TSK) die in utero at 7 to 8 days of gestation. We propose the hypothesis that Tsk might act by causing defective cell receptors with high affinity for a somatomedin-like factor promoting growth of cartilage, bone, and connective tissue and low affinity for a multiplication-stimulating factor promoting embryonic growth.