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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #153962
Title: IRON STATUS IN MICE CARRYING A TARGETED DISRUPTION OF LACTOFERRIN

Author
item WARD, P - BAYLOR COLL OF MEDICINE
item MENDOZA-MENESES, M - BAYLOR COLL OF MEDICINE
item CUNNINGHAM, G - BAYLOR COLL OF MEDICINE
item CONNEELY, O - BAYLOR COLL OF MEDICINE

Submitted to: Molecular and Cellular Biology Symposium Proceedings
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/19/2002
Publication Date: 1/1/2003
Citation: Ward, P.P., Mendoza-Meneses, M., Cunningham, G.A., Conneely, O.M. 2003. Iron status in mice carrying a targeted disruption of lactoferrin. Molecular and Cellular Biology Symposium Proceedings. 23:178-185.

Interpretive Summary: Lactoferrin is an iron-binding protein that is found in milk and body secretions. Because of the high levels of lactoferrin in milk and its ability to bind iron tightly, it has been suggested that lactoferrin is required to deliver iron to suckling offspring. To examine the function of lactoferrin in the body, mice were generated which no longer make lactoferrin (lactoferrin knockout mice). Interestingly, lactoferrin knockout pups suckling lactoferrin deficient milk from the lactoferrin knockout mothers did not suffer from iron deficiency showing that lactoferrin is not required for iron delivery to the suckling offspring. It was also shown in this study that normal adult mice do not make lactoferrin in the intestine at the site of iron absorption from the body. Consistent with the lack of production of lactoferrin in the intestine, adult lactoferrin knockout mice also had normal iron status. Collectively, these results suggest that lactoferrin is not required for iron uptake in either suckling or adult mice.

Technical Abstract: Lactoferrin is a member of the transferrin family of iron-binding glycoproteins present in milk, mucosal secretions, and the secondary granules of neutrophils. While several physiological functions have been proposed for lactoferrin, including the regulation of intestinal iron uptake, the exact function of this protein in vivo remains to be established. To directly assess the physiological functions of lactoferrin, we have generated lactoferrin knockout (LFKO-/-) mice by homologous gene targeting. LFKO-/- mice are viable and fertile, develop normally, and display no overt abnormalities. A comparison of the iron status of suckling offspring from LFKO-/- intercrosses and from wild-type (WT) intercrosses showed that lactoferrin is not essential for iron delivery during the postnatal period. Further, analysis of adult mice on a basal or a high-iron diet revealed no differences in transferrin saturation or tissue iron stores between WT and LFKO-/- mice on either diet, although the serum iron levels were slightly elevated in LFKO-/- mice on the basal diet. Consistent with the relatively normal iron status, in situ hybridization analysis demonstrated that lactoferrin is not expressed in the postnatal or adult intestine. Collectively, these results support the conclusion that lactoferrin does not play a major role in the regulation of iron homeostasis.