ABCA1 p.Ser1748Leu
| Predicted by SNAP2: | A: N (61%), C: D (75%), D: D (85%), E: D (91%), F: D (91%), G: D (71%), H: D (91%), I: D (85%), K: D (91%), L: D (85%), M: D (85%), N: D (80%), P: D (91%), Q: D (85%), R: D (91%), T: D (75%), V: D (80%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | A: N, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, T: N, V: D, W: D, Y: D, |
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[hide] Identification of three loci affecting HDL-cholest... J Lipid Res. 2009 Mar;50(3):534-45. Epub 2008 Oct 29. Juan T, Veniant MM, Helmering J, Babij P, Baker DM, Damore MA, Bass MB, Gyuris T, Chhoa M, Li CM, Ebeling C, Amato J, Carlson GA, Lloyd DJ
Identification of three loci affecting HDL-cholesterol levels in a screen for chemically induced recessive mutations in mice.
J Lipid Res. 2009 Mar;50(3):534-45. Epub 2008 Oct 29., [PMID:18974039]
Abstract [show]
We conducted a genome-wide screen using the mutagen N-ethyl-N-nitrosourea to identify recessive mutations in genes that lead to altered lipid traits in mice. We screened 7,546 G3 mice that were of mixed C57BL/6J (B6) x C3.SW-H2(b)/SnJ (C3) genomes and identified three pedigrees with differences in plasma HDL-cholesterol. Genome scan analyses mapped three distinct loci to chromosomes 3, 4, and 7. An S1748L missense mutation was identified in ABCA1 in one pedigree with undetectable levels of HDL-cholesterol and resulted in reduced protein levels. This phenotype was completely penetrant, semi-dominant, and cosegregated with high plasma triglycerides. Mice in a second pedigree had very high levels of plasma total cholesterol and HDL-cholesterol (up to 800 mg/dl total cholesterol). Despite a high degree of phenotype lability and reduced penetrance, an I68N missense mutation was identified in the transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha). Finally, a second high HDL-cholesterol pedigree of mice, again with a highly labile phenotype and reduced penetrance, was mapped to a 7 Mb locus on chromosome 3. These results illustrate the use of a hybrid background for simultaneous screening and mapping of mutagenized pedigrees of mice and identification of three novel alleles of HDL-cholesterol phenotypes.
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No. Sentence Comment
3 An S1748L missense mutation was identified in ABCA1 in one pedigree with undetectable levels of HDL-cholesterol and resulted in reduced protein levels.
X
ABCA1 p.Ser1748Leu 18974039:3:3
status: NEW240 The S1748L mutation in Abca1 recapitulates the phenotype observed in knockout mice (35-37).
X
ABCA1 p.Ser1748Leu 18974039:240:4
status: NEW243 Although the phenotype observed in S1748L mutant mice is very similar to that of the knockouts, we observed a minimal amount of protein.
X
ABCA1 p.Ser1748Leu 18974039:243:35
status: NEW246 The S1748L mutation is predicted to be located in a transmembrane domain between the V1704D and N1800H missense mutations identified in patients with Tangier disease (39).
X
ABCA1 p.Ser1748Leu 18974039:246:4
status: NEW247 Although 44 missense mutations have been identified in ABCA1, only 2 (W840R and V1704D) are expected to lie in the transmembrane domain.
X
ABCA1 p.Ser1748Leu 18974039:247:4
status: NEW241 The S1748L mutation in Abca1 recapitulates the phenotype observed in knockout mice (35-37).
X
ABCA1 p.Ser1748Leu 18974039:241:4
status: NEW244 Although the phenotype observed in S1748L mutant mice is very similar to that of the knockouts, we observed a minimal amount of protein.
X
ABCA1 p.Ser1748Leu 18974039:244:35
status: NEW