TILL: Yes. They're just easier to see in 

 the spleen. Fetal liver, which is a blood forming 

 tissue, also will make spleen colonies which 

 look very much like the colonies you get from 

 adult marrow. 



This brings up another point about fetal and 

 adult hemoglobin. I was quite interested in your 

 suggestion that you get a different number of 

 your LDH set predominating, depending on 

 whether the cells are proliferating or not, be- 

 cause this same thing has been suggested for 

 adult and fetal hemoglobin (16). It's not the 

 adult versus the fetus so much that counts; it's 

 how fast the cells are multiplying. This is 

 hard to test but it has been suggested. 



PAPACONSTANTINOU: We might be able 

 to use our system for such a test if we could 

 place fetal cells in culture and get them to dif- 

 ferentiate. 



TILL: I'm hoping we'll be able to test this 

 for fetal versus adult hemoglobin. 



GRUN: There's a possibility that you could 

 get at this question of inhibition versus the pos- 

 sibilities of supplying the missing ingredients by 

 crossing these two mice. Then, if there were an 

 inhibitory substance produced by one mouse, you 

 might expect the hybrid, also, to have this in- 

 hibitory process produced by one of the alleles. 



TILL: The trouble with the hybrid (con- 

 taining two mutant SI and two mutant W alleles) 

 is that it's got both things wrong with it. It's 

 got a defect in the cell aiid a defect in the host. 

 So it's not the same as doing a transplant. 



J. WRIGHT: Have you used hybrids? 



TILL: Hybrids have been made at The 

 Jackson Laboratory, and I believe that they 

 die right away. 



GRUN: I suppose you could try to go at it 

 by crossing the mutant with the normal. 



TILL: The cross is a different thing. The 

 transplant lets you vary the genetic composition 

 of the cell independently of the genetic composi- 



tion of the host, which you cannot do by any kind 

 of a cross that you can devise. 



KOHNE: Can the mosaics of these mice 

 live? 



TILL: That Idon'tknow about. We've essen- 

 tially made a mosaic but I don't know of a 

 naturally occurring one. Igather it is technically 

 feasible in a developing system at a very early 

 stage, after fertilization, to make a composite 

 embryo and get a mosaicthat way (17). However, 

 I don't think it's been done with these mutants. 



KOHNE: How long do the chimera live? 



TILL: Dr. Beatrice Mintz has raised them, 

 but she works primarily with a t mutation. I 

 don't think she's tried this with these mutants. 



EPEL: Are the kinetics of the iron uptake 

 in the ///cells the same as the controls once 

 it starts? 



TILL: The uptake per synthesizing cell ap- 

 pears to be the same in rapidly proliferating 

 cells from /// animals as in cells from controls. 

 The proportion of cells which are undergoing 

 synthesis is less for the cells iromf/f mice 

 than in the controls (13). 



GRUN: Maybe I'm missing a point in this 

 thing. The question that you're asking is, does 

 this Sl/Sl '* mouse form something which is in- 

 hibitory in the developing animal or not? Now, if 

 you formed an Slsl the SI allele in the het- 

 erozygote would presumably still be forming 

 inhibitory substance if there is an inhibitory 

 substance there and the SJ is a dominant con- 

 dition. 



TILL: It isn't. One sees a very nearly nor- 

 mal blood picture. Now, this suggests to me 

 that SI is failing to supply some nutritive re- 

 quirement to the stem cell rather than that SI is 

 forming an inhibitory substance. 



GRUN: In that case, in the parabiotic it 

 should have been filled. 



TILL: It might still be unstable. We were 

 very disappointed in the parabiosis experiment. 



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