al elongation and fewer TEBs compared to their *WT* littermates (Fig. [5d](#Fig5){ref-type="fig"}). *Adamts18* and *Col18a1* double-deficient (*DKO*) mice showed a further decrease in TEB numbers, fat pad filling, and branching points at 6 weeks compared to single knockouts (Fig. [5e](#Fig5){ref-type="fig"}) indicating that *Adamts18* and *Col18a1* have additive roles in ductal elongation. To assess whether this genetic interaction affects stem cell function, we serially transplanted the *DKO* epithelium. While the contralateral *WT* epithelium reconstituted glands over 5 transplant cycles, the *DKO* epithelium failed to reconstitute by the 3rd generation (Fig. [5f--h](#Fig5){ref-type="fig"}). Thus, Adamts18 and Col18a1 cooperate in mammary stem cell control, providing in vivo evidence for a role of the BM in stem cell function, likely as part of the stem cell niche.

Adamts18 modulates the ECM {#Sec8}
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To probe for structural alterations in the ECM related to *Adamts18* deletion, we used picrosirius red to stain *Adamts18*^*−/**−*^ and *WT* pubertal mammary glands. Fibrillar collagen was increased around the ducts and TEBs in *Adamts18*^*−/**−*^ relative to *WT* (Fig. [6a](#Fig6){ref-type="fig"}). Immunoblotting of protein lysates from pubertal *WT* and *Adamts18*^*−/**−*^ glands and quantification showed that levels of the important BM components, laminin and collagen IV increased 1.7- and 3.9-fold, respectively, in *Adamts18*^*−/**−*^ glands (Fig. [6b, c](#Fig6){ref-type="fig"}). Levels of the major fibrillar collagen, collagen I, were increased 6.2-fold (Fig. [6b, c](#Fig6){ref-type="fig"}). Assembly of nascent collagen I, laminin and collagen IV matrices rely on initial assembly of fibrils composed of the primordial ECM glycoprotein fibronectin, the first ECM protein to be expressed during tissue development and wound healing^[@CR40],[@CR41]^. Fibronectin levels were 3.2-fold higher in the mutants than in *WT* (Fig. [6b, c](#Fig6){ref-type="fig"}). IF showed 