AbstractLethal milk (lm) mutation in C57BL/6J inbred mice results in the reduction of zinc content in the milk and causes fatal neonatal zinc deficiency. Zinc injection to lm pups after birth helps them to overcome severe neonatal zinc deficiency and to maintain the normal body growth of lm pups. Thus, lm mutation displays a specific effect on the zinc content of the milk during lactation. The decrease in zinc content of the milk is not due to the low body zinc status in lactating lm dams. Also, oral zinc supplementation in lactating lm dams does not correct the low concentration of zinc in the milk. These findings suggest that lm mutation results in the defective cellular transport of zinc. The defective zinc transport might alter the expression of mammary genes because cellular zinc plays a critical role in diverse cellular functions. To investigate the effect of lm mutation on the expression of mammary genes, the differentially expressed cDNAs in lm mammary gland (MG) were explored using the mRNA differential display (DD) gel. One of the isolated cDNAs (M3) was expressed in the lm MG two times greater than that in the normal MG. The cloned partial M3 cDNA was shown to have the similarities to the unknown functional cDNAs in the yeast and human tissues. The M3 cDNA might have a common function in both lower and higher eukaryotes. The M3 mRNA is rich in the brain and the MG, but not in the liver and kidney. Hence, the M3 cDNA may have a certain function associated with the brain and the MG. More information regarding the cloned M3 cDNA might be provided by screening of the full length of M3 cDNA from cDNA library. J. Trace Elem. Exp. Med. 14:371–382, 2001. © 2001 Wiley‐Liss, Inc.