PMID- 10328999
OWN - NLM
STAT- MEDLINE
DCOM- 19990802
LR  - 20131121
IS  - 0888-7543 (Print)
IS  - 0888-7543 (Linking)
VI  - 57
IP  - 3
DP  - 1999 May 1
TI  - Contrasting effects of ENU induced embryonic lethal mutations of the quaking
      gene.
PG  - 333-41
AB  - Multiple alleles of the quaking (qk) gene have a variety of phenotypes ranging in
      severity from early embryonic death to viable dysmyelination. A previous study
      identified a candidate gene, QKI, that contains an RNA-binding domain and encodes
      at least three protein isoforms (QKI-5, -6 and -7). We have determined the
      genomic structure of QKI, identifying an additional alternative end in cDNAs.
      Further we have examined the exons and splice sites for mutations in the lethal
      alleles qkl-1, qkkt1, qkk2, and qkkt3. The mutation in qkl-1 creates a splice
      site in the terminal exon of the QKI-6 isoform. Missense mutations in the KH
      domain and the QUA1 domains in qkk2 and qkkt3, respectively, indicate that these 
      domains are of critical functional importance. Although homozygotes for each ENU 
      induced allele die as embryos, their phenotypes as viable compound heterozygotes 
      with qkv differ. Compound heterozygous qkv animals carrying qkkt1, qkk2, and
      qkkt3 all exhibit a permanent quaking phenotype similar to that of qkv/qkv
      animals, whereas qkv/qkl-1 animals exhibit only a transient quaking phenotype.
      The qkl-1 mutation eliminates the QKI-5 isoform, showing that this isoform plays 
      a crucial role in embryonic survival. The transient quaking phenotype observed in
      qkv/qkl-1 mice indicates that the QKI-6 and QKI-7 isoforms function primarily
      during myelination, but that QKI-5 may have a concentration-dependent role in
      early myelination. This mutational analysis demonstrates the power of series of
      alleles to examine the function of complex loci and suggests that additional
      mutant alleles of quaking could reveal additional functions of this complex gene.
CI  - Copyright 1999 Academic Press.
FAU - Cox, R D
AU  - Cox RD
AD  - Oxford University, Windmill Road, Headington, Oxford, OX3 7BN, United Kingdom.
      r.cox@har.mrc.ac.uk
FAU - Hugill, A
AU  - Hugill A
FAU - Shedlovsky, A
AU  - Shedlovsky A
FAU - Noveroske, J K
AU  - Noveroske JK
FAU - Best, S
AU  - Best S
FAU - Justice, M J
AU  - Justice MJ
FAU - Lehrach, H
AU  - Lehrach H
FAU - Dove, W F
AU  - Dove WF
LA  - eng
SI  - GENBANK/AJ012812
SI  - GENBANK/AJ012813
SI  - GENBANK/AJ012814
SI  - GENBANK/AJ012815
SI  - GENBANK/AJ012816
SI  - GENBANK/AJ012817
SI  - GENBANK/AJ012818
SI  - GENBANK/AJ012819
SI  - GENBANK/AJ012820
GR  - CA07075/CA/NCI NIH HHS/United States
GR  - CA23076/CA/NCI NIH HHS/United States
GR  - CA63677/CA/NCI NIH HHS/United States
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genomics
JT  - Genomics
JID - 8800135
RN  - 0 (DNA, Complementary)
RN  - 0 (Mutagens)
RN  - 0 (Qk protein, mouse)
RN  - 0 (RNA-Binding Proteins)
RN  - P8M1T4190R (Ethylnitrosourea)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Chromosome Mapping
MH  - DNA, Complementary
MH  - Ethylnitrosourea/*pharmacology
MH  - *Genes, Lethal
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Quaking
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Mutagens/*pharmacology
MH  - RNA-Binding Proteins/drug effects/*genetics
EDAT- 1999/05/18 00:00
MHDA- 1999/05/18 00:01
CRDT- 1999/05/18 00:00
PHST- 1999/05/18 00:00 [pubmed]
PHST- 1999/05/18 00:01 [medline]
PHST- 1999/05/18 00:00 [entrez]
AID - S0888-7543(99)95804-4 [pii]
AID - 10.1006/geno.1999.5804 [doi]
PST - ppublish
SO  - Genomics. 1999 May 1;57(3):333-41. doi: 10.1006/geno.1999.5804.