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These mice express proximal tubular dysfunction, tubular basement membrane thickening, interstitial fibrosis, and proteinuria when they are approximately 4-month old [14, 15].
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Leheste et al. initially reported that approximately 10% of the proximal tubular cells of these mice express normal levels of megalin [ 12], and Motoyoshi et al. reported residual megalin expression in 35 50% of proximal tubular cells [ 23].
Splenic B-1a cells from neonatal mice (2- 7 days) preferentially express the V3 (36 60), V5 (7183) and V2 (Q52) families that are largely located proximal to D and J gene segments, consistent with previous findings that hybridomas derived from fetal/neonatal B cells are bias in expressing proximal V5 (7183) and V2 (Q52) family genes (Perlmutter et al., 1985).
Interestingly, tg mice expressing PrP with amino-proximal deletions (named PrPΔF) show ataxia and degeneration of the cerebellar granule cell layer within a few weeks after birth [9].
Mice with floxed LKB1 exons 4 7 on both alleles (LKB1fl/fl) 34 were backcrossed with mice expressing Cre recombinase under the control of the proximal p56lck proximal promoter (Lck-Cre+), which induces Cre expression in T-cell progenitors in the thymus 35.
To delete Cdc42 in vivo in T cell lineage, Cdc42 flox/flox mice were mated with mice expressing Cre recombinase under the control of Lck proximal promoter (from Jackson Laboratory).
To investigate the relative contribution of cytosolic and nuclear Prep1 to T cell development we generated transgenic (TG) mice expressing the Pbx1NT under the control of the lck proximal promoter.
However, it is possible to generate thymocytes that selectively express PDK1 T-PDK1L155E/− T-PDK1L155E/−ckcrossing mice that express a single PDK1 L155E allele and a single PDK1 floxed allele (PDK1L155E/flΔneo) with mice expressing Cre recombynase under the control of the p56lck proximal promoter (Supplementary Figure 3).
Most convincing, the third gene MKX is in mice expressed in the condensing mesenchyme that will ultimately become the proximal ribs and vertebral bodies [ 65].
These were then backcrossed with mice expressing Cre recombinase under the control of the p56 lck proximal promoter in T cell precursors to generate PDK1 L155E /flΔneo Lck-Cre+ mice (referred to as T-PDK1 L155E /−).
(D ) Frequency of CD4+ and CD8+ T cells in the spleen of blt /+ vs blt / blt mice expressing a human BCL2 transgene (BCL2Tg) under the control of the proximal Lck promoter (left); quantification of naïve T cells from BCL2Tg blt /+ (n = 10), and BCL2Tg blt / blt (n = 10) mice (right).
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