Toward positional cloning of the curly tail gene.
BACKGROUND
The curly tail (ct) mutant mouse is one of the best-studied mouse models of spina bifida. The ct mutation has been localized to distal chromosome 4 in two independent studies and was recently postulated to be in the Grhl-3 gene.


METHODS
A recombinant BALB/c-ct strain was generated and used to precisely map the ct gene.


RESULTS
We report the absence of gross chromosomal abnormalities and the precise mapping of the ct gene to a 3-Mb region at 135 Mb (66 cM) from the centromere, closely linked to the polymorphic microsatellite marker D4Mit148. Candidate genes, Idb3, Wnt4, Cdc42, and perlecan, all localized in the critical region, were studied by sequence and expression analyses. Our data indicate that these genes in all probability do not account for the ct phenotype. In addition, our expression data do not provide strong evidence that Grhl-3 is indeed the ct gene.


CONCLUSIONS
The ct gene has not yet been identified. A total of 29 candidate genes remain present in the critical region. Refined mapping studies need to be performed to further narrow the region and additional candidate genes need to be examined. Supplementary material for this article can be found on the Birth Defects Research (Part A) website (http://www.mrw.interscience.wiley.com/suppmat/1542-0752/suppmat/2005/73/tables_S3-S6.doc).
Brouns
Madeleine R
MR
Department of Anatomy and Embryology, University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands. madeleine.brouns@ae.unimaas.nl
Peeters
Marian C E
MC
Geurts
Jan M
JM
Merckx
Diane M
DM
Engelen
John J
JJ
Hekking
Johan W M
JW
Terwindt-Rouwenhorst
Els A W
EA
Oosterbaan
Mariet E A C
ME
Geraedts
Joep P M
JP
van Straaten
Henny W
HW
D000818:Animals; D003001:Cloning, Molecular; D020732:Cytogenetic Analysis; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D008040:Genetic Linkage; D051379:Mice; D008807:Mice, Inbred BALB C; D018895:Microsatellite Repeats; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C499942:Grhl3 protein, mouse; D014157:Transcription Factors