PREPARATION OF M2 AND M16 OR KSOM  MEDIA FROM CONCENTRATED STOCKS  

TRANSGENIC FACILITY

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

600 University Ave., Toronto, Ontario, M5G 1X5

416-586-8382

GENERAL CONSIDERATIONS: 

Important note: In February 1998 we replaced the M16 medium with KSOM in all our experiment. Our preliminary data show improvement in all the applications.

MilliQ, triple-distilled or purchased ultra pure water (Gibco, BDH, Sigma) is used to prepare M2, M16 and KSOM media . 

Water that has been purified by a combination of reverse osmosis and MilliQ filtration contains minimal contaminants. Only if the conductivity is 18 megOhms or more the is the water purification system  satisfactory. Prolonged storage of water is not advised.  

Clean glass bottles that have never been exposed to detergent or organic solvents, and have been thoroughly  rinsed  
(at least 6 times in distilled water) or plastic tissue culture flasks are used to collect water and prepare stocks and media.  
Plastic ware : tissue culture bottles, flasks, polypropylene tubes, disposable pipettes are preferable.  

0.2 micron  Nalgene filter unit is used for filter sterilization. Some filter units might contain something toxic to embryos.  
First 10 - 20 ml of filtered solution are disposed or some PBS is filtered through the unit  and disposed before filtering media.  

All chemicals should be of the highest grade possible. It is often necessary to test several batches of particular component (e.g. bovine serum albumin and mineral oil). Some embryo tested chemicals might be ordered from Sigma. Chemicals used to prepare media should  be  reserved only for this purpose. 1 N NaOH, 1 N HCl  are made according to the above requirements for water and containers and  should be replaced regularly. The use of separate pH meter electrode is  suggested.  

The concentrated stock solutions can be stored at -75 C for 6 months (or -20 C for shorter time). The final working medium is filter sterilized and stored  into aliquots at +4 C  for 2-3 weeks. It is best to replace these every other week  


(Modified from " Manipulating the Mouse Embryo" A Laboratory Manual,  
Hogan  B, F. Constantini,  E. Lacy, 1986, Cold Spring Harbor Laboratory).  

COMPONENT  g / 100 ml 
STOCK A (10X)  NaCl  5.534 
KCl  0.356 
KH2PO4  0.162 
MgSO4 x 7 H2O  0.293 
Sodium Lactate  2.610 or 4.349 g of 60% syrup 
Glucose  1.000 
Penicillin G  0.060 
Streptomycin  0.050 
STOCK B (10X)  NaHCO3  2.101 
Phenol Red  0.001 
STOCK E (10X)  HEPES  5.958 
Phenol Red  0.001 
COMPONENT  g / 10 ml 
STOCK C (100X)  Sodium Pyruvate  0.036 
STOCK D (100X)  CaCl2 x 2 H2O  0.252 

PROCEDURES: 

Weigh solids into media bottles and add appropriate quantity of water. If Sodium Lactate syrup is used (stock A), the boat should be rinsed well and the wash added to the flask. For stock E add half of water volume, then adjust the pH to 7.4 with 1 N NaOH. Make up to volume using cylinder. Filter stocks through Millipore filter, aliquot into sterile tubes. 

Preparation of 100 ml of M2 and  100 ml of M16  from concentrated stocks:  
STOCK  M2 (ml)  M16 (ml) 
A (10X)  10.0  10.0 
B (10X)  1.6  10.0 
C (100X)  1.0  1.0 
D (100X)  1.0  1.0 
E (10X)  8.4 
WATER  78.0  78.0 
BSA (Bovine Serum Albumin, Sigma A4378  400 mg  400 mg 



Rinse all pipettes, tubes thoroughly into final flask. Add BSA, allow to dissolve and gently swirl the medium without excessive frothing using magnetic stirrer.  

M2:  if necessary, readjust the pH to 7.2-7.4 with 1N NaOH. Make up to volume.  
Filter sterilize and aliquot into polypropylene tubes. Store at  +4 C.  

M16: gas with 5% CO2  in air to adjust pH to 7.4, alternatively, incubate the medium for several hours (or overnight) at 37 C, 
5% CO2  with loose cap. The pH will not usually require adjustment, but it can vary with different batches of BSA .  
Make up to volume. Filter sterilize  and aliquot ino polypropylene tubes . Store at +4 C.  

To test the medium and culture conditions, collect 1 cell stage embryos (0.5 dpc) and culture them through blastocysts stage.

In February 1998 we replaced the M16 medium with KSOM in all our experiment. Our preliminary data show improvement in all the applications.