1. Nude mice have a mutation in Wnt transcription factor and in the homozygote (
ID: 88923 • Letter: 1
Question
1. Nude mice have a mutation in Wnt transcription factor and in the homozygote (nu/nu) this causes hairlessness and the absence of a thymus due to failure of the thymic epithelium to develop and differentiate. NOTE: scid mice have a mutation giving a defective DNA-dependent protein kinase (DNA-Pk) an essential part of the recombinase used for joining gene segments involving V region genes in Ig and TCR's.
a) Assuming MHC compatibility, if you gave a nude mouse (nu/nu) a thymus graft from a scid mouse (scid/scid), would the grafted animal be able to develop mature T-cells? Explain why and how?
b) If you gave the scid mouse a bone marrow transplant from the nude mouse, would this grafted animal be able to produce mature T-cells? Explain why and how ?
Explanation / Answer
a) T cells development occurs in the thymus;the thymic microenvironment directs diffrentiation as well as positive and negative selection.Two complementary defect of t cell deficiency are found in SCID(SEVERE COMBINED IMMUNE DEFICIENCY) and NUDE mice also calles athymic,they have defective thymus epithelium and lack T cells.SCID mice have a thumus but can not produce lymphocytes because of defects in enzymes required for somatic recombination.Lymphoid progenitors from nude mice can develop normally when transferred into SCID mice with a normal thymus microenvironment.
The ability of the developing T cells to make several chain rearrangement increases its chances of undergoing positive selection.MHC alleles and TCR genes are inherited independently.However it appears that TCR V gene segments are able to bind some MHC alleles,which increases the chances of positive selection.
b) Bone marrow was taken from F1 a*b mice,progeny of a MHCa parent and having both MHCa and MHCb alleles on its cells.Chimeras made by injecting bone marrow MHCa cells into MHCb animals produced T cells MHC restricted to MHCb,but they could respond to foreign antigen in the host mice because all the APC came from the MHCa bone marrow cells.This experiment shows that the bone marrow donar and recipent must share at least one MHC allele for the immune system to be able to function normally.Transgenic mice for TCR resrticted to a known MHC allele have demonstrated that T cells develop to maturity only if they recognize self MHC on the thymic epithelium.
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