Accelerated apoptosis in the Timp-3–deficient mammary gland
J. Clin. Invest. Jimmie E. Fata, et al. 108:831 doi:10.1172/JCI13171 [Go to this article.]

Figure 2
TIMP-3 regulates kinetics of mammary gland involution. (a–p) H&E–stained involuting mammary glands from wild-type (a–d and i–l) and Timp-3–null (e–h and m–p) female mice. At 1di, more cell shedding into the lumen was evident in Timp-3–deficient mammary glands (e and m) compared with controls (a and i). Lumen regression and adipose reconstitution occurred at 3di in mammary glands from wild-type mice (c and k). In contrast, lumen regression and adipose reconstitution occurred as early as 2di in mammary glands from Timp-3–null mice (f and n). Epithelial chords (epith. chord) were evident 1 day earlier (3di) in Timp-3–deficient mammary glands compared with wild-type mammary glands (compare g and o with d and l). (q) Histomorphometric analysis revealed lumen regression (solid line) was rapid between 2di and 3di in Timp-3–null mammary glands, whereas regression of lumens occurred between 3di and 4di in wild-type mammary glands. Adipose reconstitution (dotted line) was approximately 70% of the tissue by 4di in Timp-3–null mammary glands. This value was not reached until 7di in wild-type mammary glands. (r–u) At 10 days of lactation (10L) electron microscopy of secretory epithelial cells revealed that apical secretions into the lumen occurred in both wild-type and Timp-3–null mammary glands. However, at 1di these secretions (red arrows) were evident on the basal side of Timp-3–null epithelial cells within the interstitial matrix, whereas they were still only found apically in wild-type tissue. Scale bars in a–h, 100 μm, and in i–p, 50 μm; ×9,000 in r–u.