Phenotypic Mutation '18nih30a' (pdf version)
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Allele18nih30a
Mutation Type critical splice donor site (2 bp from exon)
ChromosomeX
Coordinate36,608,577 bp (GRCm38)
Base Change A ⇒ C (forward strand)
Gene Atp11c
Gene Name ATPase, class VI, type 11C
Synonym(s) Ig, A330005H02Rik
Chromosomal Location 60,223,290-60,592,698 bp (-)
MGI Phenotype Mice homozygous or hemizugous for an ENU mutation exhibit decreased B cells associated with arrested adult B cell lymphopoiesis.
Accession Number

NCBI RefSeq: NM_001001798; MGI: 1859661

Mapped Yes 
Amino Acid Change
Institutional SourceAustralian Phenomics Network
Ref Sequences
Ensembl: ENSMUSP00000033480 (fasta)
Gene Model not available
SMART Domains

DomainStartEndE-ValueType
low complexity region 78 91 N/A INTRINSIC
Pfam:E1-E2_ATPase 94 380 7e-17 PFAM
low complexity region 693 709 N/A INTRINSIC
Blast:PTPc_DSPc 737 842 N/A BLAST
low complexity region 853 865 N/A INTRINSIC
low complexity region 994 1013 N/A INTRINSIC
low complexity region 1068 1085 N/A INTRINSIC
Phenotypic Category anemia, decrease in B cells, hematopoietic system, homeostasis/metabolism, immune system, liver/biliary system
Penetrance 100% 
Alleles Listed at MGI

All alleles(4) : Gene trapped(4) 

Lab Alleles
AlleleSourceChrCoordTypePredicted EffectPPH Score
ambrosius APN X 36608577 critical splice donor site
IGL00578:Atp11c APN X 60240817 missense probably damaging 1.00
IGL01702:Atp11c APN X 60269903 missense possibly damaging 0.74
emptyhive UTSW X 60269987 nonsense
hit UTSW X nonsense
spelling UTSW X 60290036 missense probably damaging 1.00
R1551:Atp11c UTSW X 60236712 critical splice acceptor site probably null
R2134:Atp11c UTSW X 60276783 missense probably damaging 1.00
R3687:Atp11c UTSW X 60281644 missense probably benign 0.07
R3688:Atp11c UTSW X 60281644 missense probably benign 0.07
R4496:Atp11c UTSW X 60280744 missense probably damaging 0.97
Mode of Inheritance X-linked Recessive
Local Stock None
Repository

Australian PhenomeBank

Last Updated 05/13/2016 3:09 PM by Stephen Lyon
Record Created 02/07/2011 12:25 PM by Nora G. Smart
Record Posted 05/02/2011
Phenotypic Description

The 18NIH30a mutation was discovered during flow cytometry analysis of blood from ENU-mutagenized G3 mice (1)18NIH30a males exhibited B cell frequencies in blood that were decreased to 3% of controls, but normal frequencies of T and natural killer (NK) cells (2). 18NIH30a is allelic to spelling, ambrosius and emptyhive (2;3).

 

For more information on the phenotypes of 18NIH30a mice, please see the record for ambrosius.

Nature of Mutation
Figure 1. Membrane topology of P4-ATPases modeled after the structure of SERCA1 with 10 transmembrane (TM) segments and distinct actuator (A), phosphorylation (P) and nucleotide binding (N) domains. P4-ATPases are proposed to flip phospholipids to the cytosolic membrane layer. Motifs that are important for the catalytic function of P-type ATPases are indicated. Conversion of ATP to ADP by the N-domain leads to phosphorylation of the P-domain and transport of substrate. The A-domain dephosphorylates the P-domain. P4-ATPases can form complexes with CDC50 proteins (pink), which are predicted to have two transmembrane domains and a large, glycosylated ectoplasmic domain. Phosphatidylserines are indicated in dark blue, phosphatidylethanolamine in dark green, and phosphatidylcholine in orange. Although PC is typically localized to the extracellular side of the plasma membrane, it may also be a P4-ATPase substrate. The 18NIH30a mutation is located within the donor splice site of intron 26. This image is interactive. Click on the image to view other mutations found in ATP11C (red). Click on the mutations for more specific information. 

The Atp11c gene was directly sequenced in genomic DNA from 18NIH30a mice using Sanger sequencing and a T to G transversion was detected at position 34148572 in the Genbank genomic region NC_000086 for the Atp11c gene on chromosome X (GTTAGATTTT-> GGTAGATTTT). The mutation is located within the donor splice site of intron 26, two nucleotides from the previous exon.  Atp11c contains 30 total exons.  Multiple Atp11c transcripts are displayed on Ensembl and Vega. The effect of the mutation at the cDNA and protein level is unknown.  One possibility, shown below, is that aberrant splicing may result in skipping of the 66 base pair exon 26 and in-frame splicing from exon 25 to exon 27.  This would result in deletion of 22 amino acids encoding the majority of the eighth transmembrane domain of the ATP11c protein.

 

     <--exon 25   <--exon 26 intron 26--> exon 27-->  <--exon 30    

      AATGGAAAG…………ACTCTGAAG GTTAGATTT…………CTCGCCTTG…………ATATTGTAA

1428  -N--G--K-…………-T--L--K-              -L--A--L-…………-I--L--*

       correct      deleted                      correct

 

The donor splice site of intron 26, which is destroyed by the mutation, is indicated in blue; the mutated nucleotide is indicated in red.

 

Please see the record for emptyhive for information about Atp11c

Putative Mechanism

The 18NIH30a mutation likely results in aberrant splicing of the Atp11c transcript.  The phenotypes of these mice are essentially identical with other Atp11c mutants.

Primers Primers cannot be located by automatic search.
References
Science Writers Nora G. Smart
Illustrators Diantha La Vine
AuthorsMehmet Yabas, Charis E. Teh, Sandra Frankenreiter, Dennis Lal, Carla M. Roots, Belinda Whittle, Daniel T. Andrews, Yafei Zhang, Narci C. Teoh, Jonathan Sprent, Lina E. Tze, Edyta M. Kucharska, Jennifer Kofler, Geoffrey C. Farell, Stefan Broer, Christopher C. Goodnow, Anselm Enders
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Edit History
05/25/2011 10:01 AM (current)
05/25/2011 9:55 AM
05/02/2011 3:10 PM