Question

1. Explain what do each of the genotype mean

• p53 ^+/-
• p53 ^-/-
• K-ras^LA1;p53 ^+/-
• K-ras^LA1;p53 ^-/-

Answer 1

1. a. p53+/-: This genotype indicates that the mouse is a heterozygous mutant mouse of p53. In this animal/cell, the cell expresses one wild type allele of p53 gene as indicates by ‘+’. The other allele of p53 is the mutant allele, and hence indicated by ‘-‘. Hence, p53 protein produced is only 50%. The p53 gene, a tumor suppressor gene is involved in DNA repair and inhibits cell cycle when DNA is mutated. It promotes apoptosis in cells

b. p53-/-: This genotype is of animal or cell where both allele are mutated, giving non-functional protein. Thus, there is no wild type allele and hence, wild type p53 is not produced in the cell.

c. K-rasLA1; p53 +/-: This genotype indicates that the cell expresses a latent mutant K-ras allele at an endogenous locus. This latent mutant K-ras can be activated spontaneously when present in vivo. The latent allele is added to the genome by recombination artificially. Hence, there is only one copy of this mutant Kras allele (not two copies).The p53+/- indicates that the mouse is heterozygous for p53. It has one wild type and one mutant allele of p53. The mutant allele does not produce functional allele. Mice which are K-rasLA1; p53 +/- will show progression to cancer (adenocarcinoma), with decreases survival of cells. Kras is an oncogene and this later form will cause activation of cell cycle. As p53 is produced in low amounts, apoptosis will still be seen but cannot kill all proliferating cells.

d. K-rasLA1; p53 -/-: This genotype indicates that there is one allele of latent Kras introduced. It also has two copies of mutant p53 alleles, which lead to production of non-functional p53. The latent Kras will lead to oncogenesis due to increased proliferation. As no functional p53 is produced, the cell will not undergo apoptosis. This will lead to much accelerated progression to cancer.