The mouse Nell1 cDNA and amino acid sequences are disclosed. Also disclosed is a Nell1 knock-out mouse with several bone- and cartilage-related defects. On the molecular level, the loss of Nell1 function led to reduced expression of certain extracellular matrix proteins. The disclosure here provides new tools for studying bone and cartilage development as well as new drug screening and treatment strategies for bone- and cartilage-related diseases and conditions.