Biology 52 problem set C; Mammalian development and genetic engineering; Cancer

(* = hand in answer in recitations.)

22) How well-suited is each of the following animals as a model to study developmental biology? In each case, for study of which stages of development or developmental processes would the organism be useful, and what experimental approaches would be most suitable? What drawbacks would each have as an experimental model?

a) Xenopus; b) zebrafish; c) mouse; d) elephant

23) How many fertilization events give rise to identical twins in mammals?

24) Which of the following cells in a mouse embryo contributes to the adult mouse?

trophoblast

hypoblast

epiblast

inner cell mass

25) At the 8-cell stage, a mouse embryo with a genotype conferring red fur color is fused with a similar embryo with a genotype conferring green fur color. The fused embryo is reimplanted into a foster mother with white fur. Assume that white fur arises from a complete absence of genes for pigments, and that the red and green embryos are homozygous for all alleles of their respective pigment genes.

a) What fur color(s) can the progeny mouse have (list all possibilities)?

b) If the progeny mouse from part a) is mated with a mouse with white fur and has children, what color(s) can the offspring be? List all possibilities.

26) Outline the steps one would take to construct a mouse with a mutation in a particular cloned gene X.

27) What phenotypes do the following mutations cause?

a) gridlock mutation in zebrafish

b) lim1 mutation in mouse

In each case, what is the normal function of the mutated gene in development?

28) What is a stem cell? Why is there interest in stem cells obtained from adult tissues?

*29) Suppose that a particular signaling molecule of the TGF-b class can induce cultured mouse ES cells to differentiate into a mesodermal cell type. Suggest experiments that would test whether this signal is i) necessary and ii) sufficient to induce mesodermal development in normal mouse embryos. Take into account the types of experiments that are practical in the mouse. Describe both the methods and the possible expected outcomes of the experiments.

30) Suppose a gene encoding almost the same molecule as in question 29 is also present in Xenopus. How would you test whether the product of this gene is a signal that induces mesodermal development in Xenopus?

31) In cases in which exposure to mutagens causes cancer, the disease usually occurs years after the exposure. Why is this?

32) a) Describe a phenotypic change that occurs in a colon cell upon forming a pre-cancerous polyp.

b) Describe a phenotypic change that occurs in a pre-cancerous polyp cell in the colon that then forms a metastatic cancer cell.

c) What kind of events occur in colon cells to cause these phenotypic changes?

33) People with hereditary non-polyposis colon cancer (HNPCC) have a predisposition to develop cancer.

a) Are these people born with cancer?

b) What biochemical deficiency do these people have?

c) Why do they develop cancer of the colon rather than of other tissues?

34) Early in development, mutant mouse embryos homozygous for a recessive mutation in the Rb gene develop lens cells that fail to differentiate properly, and instead proliferate (divide) too much. Many apoptotic (dying) cells are also seen in the vicinity of these proliferating cells. If the same mice are also mutant in the p53 gene, there is still excess cell division but apoptotic cells are not present.

a) What does the wild-type Rb protein do in a normal lens cell?

b) What is the wild-type p53 protein doing in lens cells in the rb mutant background?

c) In studying immunity, one can destroy the immune system of a mouse by treating the mouse with X-rays. In a mouse lacking p53, X-irradiation does not destroy the immune system. Why not?