Question $6..$ Mutations in the human gene HEXA, or H $,$ cause the autosomal recessive disorder Tay Sachs disease. To create a mouse model of Tay Sachs disease, you want to generate a disrupting construct, in which a gene conferring colchicine resistance has been inserted into the mouse H gene. Colchicine usually kills mouse embryonic stem cells $($ES$)$ cells. You introduce the disrupting construct into ES cells.

A$)$ What type of ES cells do you want to generate by introducing the disrupting construct?

a$)$ colchicine$-$resistant cells in which the disrupting construct has recombined homologously into the genome at the H locus

b$)$ colchicine$-$sensitive cells in which the disrupting construct has recombined homologously into the genome at the H locus

c$)$ colchicine$-$sensitive cells in which the disrupting construct has recombined nonhomologously into the genome

d$)$ colchicine$-$resistant cells in which the disrupting construct has recombined nonhomologously into the genome

b$)$ The ES cells you generated above came from true$-$breeding mice with fur $($F$),$ also called furred. To create chimeric F$1$ mice, you introduce these ES cells into embryos that are homozygous for the recessive f allele and therefore are nude and have no fur. Chimeric mice that have taken up your genetically modified ES cells can be identified as having have patches of fur and no fur. What is the genotype with regard to the F gene and the HEXA gene of the patches with fur and no fur? Use H for the wildtype HEXA allele and $h$ for the mutated HEXA allele.

nude patches with no fur

patches with fur

c$)$ How would you generate mice in which all cells contain your disrupted HEXA gene?

i$)$ you should mate your chimeric F$1$ mice with furred mice of the genotype F$/$F All of the furred F$2$ mice will carry the mutation.

ii$)$ you should mate your chimeric F$1$ mice with nude mice of the genotype f$/$f$.$ All of the furred F$2$ mice will carry the mutation.

iii$)$ you should mate your chimeric F$1$ mice with furred mice of the genotype F$/$F$.$ Half of the furred F$2$ mice will carry the mutation.

iv$)$ you should mate your chimeric F$1$ mice with nude mice of the genotype f$/$f$.$ Half of the furred F$2$ mice will carry the mutation.

v$)$ None of the above