GENIC ACTION IN THE MOUSE 221 



deviation present at an especially early stage when other reactions are still normal. 

 This concept underlies some of the especially promising current investigations on 

 murine muscular dystrophy, but the answers are not yet forthcoming. 



GENES, HORMONES, AND PATTERNS OF RESPONSE 



Localizing the initial site of genie action presents special problems in cases of 

 endocrine defect, because of reciprocal relations between different hormones. This has 

 proved particularly true in recent studies of pituitary dwarfism in the mouse, the first 

 gene whose action was analyzed by substitution therapy. 1222, 1236 The defect is 

 definitely in the anterior pituitary, but the particular type of cell primarily affected is 

 still in doubt to some extent. Gonadotrops are present, although abnormal in ap- 

 pearance, in the dwarf pituitary, and their functional capacity has been proven con- 

 clusively in transplantation experiments. 1223 All observers agree dwarfs show a great 

 deficiency in typical murine acidophils, but recent investigations using sophisticated 

 histologic techniques 321, 100 °- 1049, 1368 disagree as to whether there are undifferentiated 

 potential acidophils. There is also great reduction in typical thyrotrop cells. Uptake 

 of radioactive iodine suggests but does not prove that the thyroid of dwarfs is especially 

 sensitive to thyrotropin, which favors the interpretation of initial deficiency of thyro- 

 trops and thyrotropin. 1367 Recent experiments in which rate of growth was studied 

 following reciprocal transplants placing pituitaries of littermate normal and dwarf 

 mice 14 to 18 days of age into the sella of hypophysectomized normal and dwarf hosts 

 showed a comparable rate of growth of normals and dwarfs with transplanted normal 

 pituitaries and a reduced rate in normals with dwarf pituitaries. 155 This evidence 

 indicates the defect is in the pituitary rather than the hypothalamus, since the organ 

 functions autonomously following transplantation. It also favors the interpretation 

 of primary deficiency of acidophils and growth hormone. It is to be hoped that in the 

 near future a transplantation approach, combined with histologic study of changing 

 cellular types in the implanted pituitary, may help to identify the types of pituitary cell 

 initially affected in dwarf mice. 



Genetically controlled differences between inbred strains have also been reported 

 for androgen level and responses, 189, 191, 192, 194 estrogen level and response, 191 and 

 thyroxin level and response. 190, 193 Since these differences have a polygenic basis, 

 they do not provide good material for retrograde analysis, but the methods used merit 

 description. Secreting glands were extirpated or inactivated, and sensitivity of target 

 organ measured by addition of graded doses of exogenous hormone. Normal circu- 

 lating level of each hormone was calculated from the dosage producing the end-organ 

 condition normal for the strain. 



There is also much evidence of genetically controlled difference in reaction of 

 the adrenal to gonadectomy. The adrenals of some strains fail completely to 

 respond to this stimulus, others show hyperplasia, and still others show cortical 



carcinoma 



193, 271. 1407. 1408 



