PMID- 15070709
OWN - NLM
STAT- MEDLINE
DCOM- 20040527
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 103
IP  - 8
DP  - 2004 Apr 15
TI  - Identification of quantitative trait loci that modify the severity of hereditary 
      spherocytosis in wan, a new mouse model of band-3 deficiency.
PG  - 3233-40
AB  - Defects in red blood cell (RBC) membrane skeleton components cause hereditary 
      spherocytosis (HS). Clinically, HS varies significantly even among individuals 
      with identical gene defects, illustrating the profound effects of genetic 
      background on disease severity. We exploited a new spontaneous mouse model, wan, 
      which arose on the inbred C3H/HeJ strain, to identify quantitative trait loci 
      (QTL) that modify the HS phenotype. Homozygous wan mice have severe HS due to a 
      complete deficiency of erythroid band 3. A QTL analysis of RBC count, hemoglobin, 
      hematocrit, mean corpuscular volume (MCV), and mean corpuscular hemoglobin 
      content (MCHC) was performed in wan/wan mice from an F2 intercross between 
      C3H/HeJ(+/wan) and CAST/Ei(+/+) F1 hybrids. Hematologic and survival data from 
      C3H, CAST/Ei F2 wan homozygotes support the hypothesis that genetic modifiers 
      significantly influence the band-3 null HS phenotype. Significant QTL were 
      identified for the MCV trait only, suggesting that RBC membrane characteristics 
      are a target for modifier gene action. The most significant quantitative trait 
      locus, Hsm1 (hereditary spherocytosis modifier 1), localizes to mouse Chromosome 
      12 and is dominant. The peak LOD score was obtained with a marker for Spnb1 
      encoding erythroid beta-spectrin, an obvious candidate gene.
FAU - Peters, Luanne L
AU  - Peters LL
AD  - The Jackson Laboratory, Bar Harbor, ME 04609, USA. luanne@jax.org
FAU - Swearingen, Rebecca A
AU  - Swearingen RA
FAU - Andersen, Sabra G
AU  - Andersen SG
FAU - Gwynn, Babette
AU  - Gwynn B
FAU - Lambert, Amy J
AU  - Lambert AJ
FAU - Li, Renhua
AU  - Li R
FAU - Lux, Samuel E
AU  - Lux SE
FAU - Churchill, Gary A
AU  - Churchill GA
LA  - eng
GR  - RR01183/RR/NCRR NIH HHS/United States
GR  - DK34083/DK/NIDDK NIH HHS/United States
GR  - R01 HL064885/HL/NHLBI NIH HHS/United States
GR  - CA34196/CA/NCI NIH HHS/United States
GR  - HL64885/HL/NHLBI NIH HHS/United States
GR  - HL32262/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20031230
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Anion Exchange Protein 1, Erythrocyte)
RN  - 0 (Blood Proteins)
RN  - 0 (Codon, Terminator)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (erythrocyte membrane band 4.2 protein)
RN  - 12634-43-4 (Spectrin)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Anion Exchange Protein 1, Erythrocyte/*deficiency/*genetics
MH  - Base Sequence
MH  - Blood Proteins/deficiency
MH  - Codon, Terminator
MH  - Crosses, Genetic
MH  - Cytoskeletal Proteins
MH  - DNA/genetics
MH  - Disease Models, Animal
MH  - Erythrocyte Indices/genetics
MH  - Humans
MH  - Lod Score
MH  - Membrane Proteins
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Mutant Strains
MH  - Phenotype
MH  - *Quantitative Trait Loci
MH  - Spectrin/genetics
MH  - Spherocytosis, Hereditary/*blood/*genetics
EDAT- 2004/04/09 05:00
MHDA- 2004/05/28 05:00
CRDT- 2004/04/09 05:00
PHST- 2004/04/09 05:00 [pubmed]
PHST- 2004/05/28 05:00 [medline]
PHST- 2004/04/09 05:00 [entrez]
AID - S0006-4971(20)43826-1 [pii]
AID - 10.1182/blood-2003-08-2813 [doi]
PST - ppublish
SO  - Blood. 2004 Apr 15;103(8):3233-40. doi: 10.1182/blood-2003-08-2813. Epub 2003 Dec 
      30.