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Title: EXPRESSION OF LYSOSTAPHIN IN MILK OF TRANSGENIC MICE AFFECTS THE GROWTH OF NEONATES

Author
item MITRA, ABHIJIT - INDIAN VET RES INSTITUE
item Hruska, Kathleen
item WELLNITZ, OLGA - UNIVERSITY OF VERMONT
item KERR, DAVID - UNIVERSITY OF VERMONT
item Capuco, Anthony
item Wall, Robert

Submitted to: Transgenic Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/1/2003
Publication Date: 12/1/2003
Citation: Mitra, A., Hruska, K., Wellnitz, O., Kerr, D. E., Caupuco, A. V., and Wall, R. J. (2003). Expression of lysostaphin in milk of transgenic mice afftects the growth of neonates. Transgenic Research 12:597-605

Interpretive Summary: Mastitis is a serious and costly disease of dairy cows. This inflammation of the mammary gland is primarily caused by bacterial infection; 15-30% of all mastitis cases are traced to a particular species of bacteria, Staphylococcus aureus. As an initial step towards making dairy animals more resistant to S. aureus infection, we generated genetically-engineered mice(BLG-Lys) that produce an antimicrobial protein in their milk. This protein, called lysostaphin, specifically kills Staphylococcus bacteria. Production of lysostaphin in the milk effectively protected the mammary glands of the BLG-Lys mice from an introduced infection of S. aureus. In the current study, we have investigated mammary gland development and function in the BLG-Lys mice. As we bred more of the BLG-Lys mice for our studies, there was a tendency for fewer of the BLG-Lys litters to survive to weaning age when compared to litters of other laboratory mice. When ordinary pups were removed from their birth mothers and nursed by BLG-Lys females, the pups gained weight more slowly than pups nursed by ordinary females. The weights at weaning age also were decreased for pups nursed by BLG-Lys females compared to those pups delivered and nursed by ordinary females. The growth retardation was temporary, however, because the pups carrying the BLG-Lys gene reached their full weight by adulthood. These observations suggested that the mammary glands of the BLG-Lys females might be impaired and not producing enough milk for the pups. When we measured milk production, however, there was no difference detected between BLG-Lys and ordinary females. Furthermore, the tissue structure of the mammary gland did not differ between the two groups. The milk itself also was normal when analyzed for protein and fat content. The results clearly indicate that the mammary glands of BLG-Lys females are fully functional and are not responsible for the initial reduced growth of pups.

Technical Abstract: As an initial step towards enhancing mastitis resistance in dairy animals through transgenesis, we previously generated BLG-Lys mice. These mice secrete lysostaphin, a potent anti-staphylococcal protein, in their milk. In the current study, we continue our assessment of lysostaphin as a suitable antimicrobial protein for mastitis resistance and have investigated mammary gland development and function in three lines of transgenic mice. As the lines were propagated, there was a tendency for fewer BLG-Lys litters to survive to weaning (51% as compared to 90% for nontransgenic lines, p = 0.080). Nontransgenic pups fostered on dams from these three lines exhibited diminished growth throughout the lactation period. Weaning weights were also decreased for pups nursed by transgenic dams (15.35 ± 0.27 gm) when compared to transgenic pups cross fostered and nursed by nontransgenic dams (18.61 ± 0.61 gm; p < 0.001). Milk production at peak lactation was not different between BLG-Lys and nontransgenic dams. Furthermore, mammary gland histology and b-casein expression during the initial establishment of lactation did not differ significantly between transgenic and nontransgenic dams. The results suggest the reduced growth of neonates on BLG-Lys dams is not attributable to impaired mammary development or function.