In mice the ability to run normally is a dominant trait - what fuctioning
Chr, Chromosome. TADs mark segments along a chromosome that share a common regulatory mechanism. Data from Dixon et al. Taken together, two major observations stand out from our genomic survey. One, a polygenic, infinitesimal selection model with strong LD among marker SNPs performed better than moderate LD or no LD Figure 1—figure supplement 2E ; and two, we nevertheless find more discrete loci in LS1 and LS2 than in Ctrl, beyond the significance threshold set by the infinitesimal model Figure 2 ; Figure 2—figure supplement 2. in mice the ability to run normally is a dominant trait
In order to explore the role of these mormally acids both in vitro and in vivo, cytoplasmic mutants of the murine H-2 Kb gene were constructed and expressed in murine L cell fibroblasts and transgenic mice. In L cell fibroblast transfectants, Kb mutant molecules reached higher cell surface levels than Kb wild-type KbWT molecules and demonstrated a higher capacity for binding exogenously-added peptides.
In the transgenic mice, FACScan analysis of peripheral blood leukocytes and splenocytes revealed that cytoplasmic mutant Kb molecules reached significantly higher surface levels compared to wild-type Kb and interfered less with endogenous class I maturation and surface expression. Constitutive endocytosis of class I molecules from the surface of activated T cells was also shown to be significantly impaired by cytoplasmic point mutations.
The results demonstrate that the conserved tyrosine and serine residues are important for regulating lymphocyte and fibroblast MHC class I cell surface expression both in vitro and in vivo, and provide evidence of an inducible tyrosine-based endosomal targeting motif in the cytoplasmic tail of class I molecules. The functional studies suggest that the tyrosine motif in particular may be important for the generation of class I-restricted CTL responses in vivo.]
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