17 July 2012
Technion researchers headed by Prof. Yehuda G. Assaraf and the doctoral student Inbal Lasry of the Faculty of Biology, in collaboration with researchers from the Sheba Medical Center, have identified and characterized a mutation in breastfeeding mothers which leads to zinc-deficient milk and could in turn cause serious health problems in exclusively breastfed Infants. These findings were published in the scientific Journal of Biological Chemistry and have garnered substantial interest, as breast milk is perceived as always being healthy for the infant.
"Zinc is a mineral which plays an essential role in growth and development processes, including the development of cognitive and motor functions of the brain as well as the proper function of the immune system and the skin. Thus, zinc is a highly essential mineral particularly for infants, as they undergo accelerated growth and development processes", explains Prof. Assaraf, head of the Fred Wyszkowski Cancer Research Laboratory in the Faculty of Biology at the Technion. "A large number of proteins in our body relies on zinc for their normal function", adds Prof. Assaraf. Zinc deficiency could lead to rashes and dermatitis that have the appearance of severe burns; it could alos lead to diarrhea, hair loss, loss of appetite, impaired function of the immune system and impaired function of the nervous system". Thus, for example, zinc deficiency could impede our ability to defend ourselves, through the immune system and the inflammation process, against foreign pathogens such as bacteria, viruses, and parasites.
The research was conducted in collaboration with a team from the Edmond and Lily Safra Children's Hospital in the Sheba Medical Center, headed by Dr. Yair Anikster, Director of the Pediatric Metabolic Diseases Unit. The research began with the referral, by Soroka University Medical Center and Bikur-Holim Hospital, of two infants from two different Israeli families who suffered, among others, from an especially severe rash which has the appearance of a severe burn. Blood tests and breast milk analysis led to the hypothesis that the illness is due to zinc deficiency, and this in turn led the researchers to examine the sequence of the ZnT-2 gene. The importance of the ZnT-2 transporter is critical during the breastfeeding period because it acts as a transporter which delivers zinc from the mother's blood to the breast milk on which the infant feeds. The researchers identified in the mothers, a specific mutation in the ZnT-2 gene in a highly evolutionarily conserved region, that appeared essential for the preservation of the proper structure and function of this zinc transporter protein. "We have discovered that the mutation in the ZnT-2 zinc transporter disrupts its activity, and this consequently prevents the transport of zinc to the breast milk. As a result, an infant who is exclusively breastfed and who does not receive any food supplement does not receive the appropriate zinc levels, which in turn leads to disease", explains Prof. Assaraf. This part of the research was conducted in collaboration with Prof. Shannon L. Kelleher of Pennsylvania State University, USA.
"Every gene has two genetic components known as alleles – one originates from the father and the other from the mother. In the present disease – one of the two alleles was defective. Supposedly, the second, healthy allele, being entirely normal, should have protected the infant from this defect", explains Prof. Assaraf. The Technion researchers have found an answer to this scientific-medical dilemma: the current research made the discovery that the ZnT-2 zinc transporter operates as a couple known as a dimer, namely: two identical ZnT-2 proteins couple to create the mature, active zinc transporter which transfers zinc from the mother's blood to the breast milk. Therefore, if one of these proteins is impaired – the zinc transporter becomes inactive. That is, even a single mutation, either in the paternal allele or in the maternal one, is sufficient to shut the zinc transporter down, a phenomenon known in the scientific language as a dominant negative effect.
This discovery paves the way for pre-pregnancy genetic screening in women, toward providing them with genetic counseling to clarify to those of them who harbors the defective gene that while they are breastfeeding, they will have to provide their baby with a zinc-containing food supplement, in order to avoid health problems to the infant. Among others, the researchers are currently examining the prevalence of the mutations in the ZnT-2 gene.