Transgenic Animals and Lactation

Transcription

1 Transgenic Animals and Lactation

2 Application of transgenic technology to lactation Introduce new proteins to give specific changes Animal growth & health Bacteria levels Processing properties Fat content/type Amount of protein

3 UCD first to demonstrate the functional and physical properties of milk can be altered by the transgenic approach Expressed human lysozyme in mouse milk Made lysozyme at 0.4 mg/ml under the control of the bovine α s1 -casein gene Followed lactation curve Faster rennet clotting time and stronger curd Slowed growth of mastitiscausing and cold spoilage bacteria Maga et al Transgenic Res 3:36-42 Maga et al J Dairy Sci 78: Maga et al J Food Prot 61:52-56

4 What about a real animal? Non-bioreactor transgenic animals for lactation Source Promoter Gene Species U. Illinois M. Wheeler 2002 bα-lac bα-lac Pig 2005 bα-lac higf-i Pig UC Davis E. Maga 2004 gβ-lg rscd Goat 2006 bαs 1 hlysozyme Goat USDA B. Wall 2005 oβ-lg Lysostaphin Cattle New Zealand G. Laible 2003 bβ-cn bβ/κ-casein Cattle

5 Hypothesis: Animal Growth & Health Faster growth Greater pre-weaning gain Maintenance of growth during illness Improved disease resistance, immune factors

6 Transgenic pigs and lactation More α-lactalbumin To increase milk production IGF-1 Transgenics make more lactose (and milk) and pigs grow faster Intestinal development Increased musocal weight and enzyme activity Noble et al J Anim Sci 80: Monaco et al Transgenic Res 14:

7 Hypothesis: Fat Content/Type Short chain, saturated fatty acids If enzyme added to modify existing fat: Change ratio of bad fat to good Milk more healthy for human consumption Novel flavors Novel products

8 Stearoyl-CoA desaturase in the mammary gland The type of fat in milk is modified Transgenic goats make less SFA and more MUFA and PUFA Total amount of fat remains the same Transgenic goats make more CLA Disease resistance implications Percentage change in milk fat composition #34 #37 #53 SFA MFA PUFA Reh et al J Dairy Sci 87:

9 Hypothesis: Processing Properties/Amount of Protein in Milk If protein with positive charge is made in milk: Increase protein interactions Promote faster RCT Increase gel strength Affect micelle size Novel processing properties Novel products If more protein was made in mammary gland: More food for animal and human consumption Increase cheese yield/lactation Modify processing properties Benefits producers and processors

10 Transgenic β- and κ-casein cows To influence milk processing and overall protein levels 11.2 mg/ml κ-casein 15.8 mg/ml β-casein Altered κ-casein:total casein ratio Color change Amount of fat and minerals also affected Brophy et al Nat. Biotechnol. 21:

11 Hypothesis: Animal Growth & Health Improved disease resistance Mastitis Scours

12 Transgenic dairy cattle and mastitis Lysostaphin transgenic cows Bacterial-derived hydrolase Mastitis challenge: 71% control glands infected 14% transgenic glands infected Effective against S. aureus only! Wall et al Nat. Biotechnol. 23:

13 Hypothesis: Bacteria Levels Types of bacteria in milk Cold-spoilage Lactic acid Mastitis-causing If an antimicrobial is made in milk: Decrease overall level of bacteria in milk -Stop/slow cold spoilage of milk -Stop/slow outbreaks of human illness from milk Affect cheese making??? Slow/stop infection in udder Mastitis protection

14 Human lysozyme transgenic goats Potential benefits: Expressed in goat milk at levels of 270 µg/ml 68% of human milk Healthier udder Changes in processing properties Anti-microbial activity 20 kda 14 kda HLZ Maga et al J Dairy Sci 89:

15 Anti-microbial activity: Improved animal/udder health Somatic Cell Count (cells/100ml) Parity 1 st Transgenic 291,00 Herd 351,000 2 nd 208, ,000 3 rd 409, ,000 All 284, ,000* P<0.05

16 Processing properties Decreased rennet clotting time Increased curd strength Implications for cheese manufacturing, types of cheese that can be made Curd Strength Curd Strength Applied Stress (Pa)

17 Anti-microbial activity: Lysozyme goat milk slows the growth of some bacteria Transgenic milk was bacteriostatic E. coli S. aureus P. fragi S. cohnii Corynebacteria spp. Transgenic milk has increased shelf life Maga et al Foodborne Pathog Dis 3:

18 Transgenic vs Additive Inhibition of E. coli growth Added Lysozyme Added Lactoferrin Transgenic Reduction in Bacterial Growth

19 Antimicrobial activity: Potential to improve human health Pig Intestinal coliforms (CFU/gram) Upper Lower Transgenic-Fed ,400 1, ,400 Control-Fed ,900 5,600, ,600 17, ,000 3,980, , Maga et al Transgenic Res 15:

20 Future Work Desaturase expression Generation of lactoferrin transgenic goats First lactation started last week! Impact of lysozyme milk on: Mastitis Processing Disease prevention Gut development

21 Artemis the Goat