| First Author | Charles DJ | Year | 1984 |
| Journal | Mouse News Lett | Volume | 71 |
| Pages | 37-38 | Mgi Jnum | J:13991 |
| Mgi Id | MGI:62169 | Citation | Charles DJ, et al. (1984) Research News. Mouse News Lett 71:37-38 |
| abstractText | Full text of MNL contribution: Research News. 1. Offspring of mutagen treated sires are screened for enzyme activity mutants in order to determine germ cell mutation rates in experimental animals. Male (101/ElxC3H/El)Fl mice are treated with agents such as X-rays, ethylnitrosourea (EMU) or procarbazine hydrochloride, and then mated to untreated T-stock females, homozygous at 7 recessive loci. At 3 weeks of age, the offspring are scored for recessive specific locus and dominant cataract mutations (EHLING, Arch. Toxicol. 1980). A portion of the offspring, 4-6 weeks old, is further examined for enzyme charge and enzyme activity mutants. To date, 33 independant enzyme activity mutants have been recovered descendent from postspermatogonial or spermatogonial treated cells; 18 caused reduced activity (3 LDH, 4 TPI, 3 HDH, 2 GPI, 3 GAPDH, 2 G6PD, 1 GR), and 15 caused enhanced activity (1 TPI, 1 MDH, 6 PGAM, 4 PK, 3 GR). One mutant (No. 10683) with PK hyperactivity and one mutant (No. 10168) deficient for G6PD, detected in offspring of ENU (250 mg/kg) treated sires, have been further characterized. For the PK mutant, the activity alteration detected in the blood could also be found in the liver, but not in the muscle, kidney, heart, spleen, lung nor brain. Heterozygous mutants have erythrocyte PK activity enhanced up to about 160% and homozygous mutants up to about 240%, as compared to homozygous wild types. The mutation is codominantly expressed. The heterozygous and homozygous mutants are viable and fully fertile, and do not show symptoms of erythrocytosis. The mutation does not affect the heat stability, the electrophoretic mobility nor the Km (for phosphoenolpyruvate) of the PK molecule. It is suggested that the regulatory locus of Pk-1 is affected by the mutation. The observations support also the theory of one structural locus for the erythrocyte and liver isozymes. (This mutant has been sent to Dr. Grahame BULFIELD, Poultry Research Centre, Midlothian, U.K., for further studies on the regulatory mechanisms of PK. A paper describing this PK mutant is in press in Biochemical Genetics.) The G6PD mutant is the first isolated among experimental animals at the X-chromosomal G6PD locus. Hemizygous, heterozygous and homozygous mutants have respectively roughly 20%, 60%, and 15% G6PD rest activity in the blood. The heat stability of the G6PD molecule is the same in all genotypes. The activity reduction of G6PD is also observed in other tissue extracts. Haematological parameters such as haemoglobin content, erythrocyte number, haematocrit percent, spleen weight, and serum bilirubin did not show significant differences between mutants and wild types. Spleen weight in the hemizygotes was however enhanced by a factor of about two. (This mutant has been given to Dr. Josephine PETERS, MRC, Harwell, U.K., for mapping on the X-chromosome.) (Daniel J. CHARLES and Walter PRETSCH). |
