International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

B12. Mouse Homologue of the Drosophila pellino Gene, Pli1 on Chr 11 is Affected in the Wobbler Mutant

Schmitt-John, T., Resch, K., Wiegand, C., Fuchs, S., Jockusch, H.,
Developmental Biology & Molecular Pathology, University of Bielefeld, Germany, E-mail:

The wobbler (wr) mutation of the mouse causes degeneration of spinal motoneurons and a defect of spermiogenesis. No functional candidate gene could be deduced from the pathophysiology of WR (wr/wr) mice, therefore we set out to search for the wr gene(s) by positional cloning. The wr-critical region was mapped to proximal mouse Chr 11 a region homologous to human Chr 2p13.3, as characterised by RH-mapping and YAC/BAC contigs [1]. Several positional candidate genes were defined, of these, Meis1, Rab1a, Arp2, and Slc1a4 have subsequently been excluded by rare recombination events; others, Otx1, Mor2, and Udpg2, appeared unlikely on the basis of sequence analysis, knock out phenotype (Otx1, [2]), and enzyme assays (Mor2, Udpg2).

One of the remaining few candidates was identified as a mouse homologue of the Drosophila gene pellino, Pli, a cytoplasmic factor involved in the dorsal/pelle pathway [3]. Two isogenes of Pli have been identified in mouse/man, Pli1 on Chr 11/2p, the candidate for wr, and Pli2 on Chr 14. With RT-PCR, transcripts of Pli1 and Pli2 were found in all tissues tested. A polyclonal antibody against Drosophila Pellino protein stained a 48 KDa band in immunoblots of wildtype mouse testis and a 22 KDa band in skeletal muscle, but gave no signal with other tissues. In WR mice, the RNA signals were indistinguishable from WT but the protein signal in testis was absent, whereas the muscle signal was not affected. These findings strongly suggest that a Pli1 mutation is responsible at least for the testis phenotype of WR, although the DNA sequence of the Pli1 protein coding region from WR was found to be identical to WT. We suspect that the still undetected wr mutation somehow blocks the translation of the Pli1 message. To finally prove the identity of wr and Pli1, the appropriate knock-out and transgenic rescue experiments are being performed.

We thank Dr J. Grosshans (Princeton) and F. Schnorrer (Tübingen) for providing anti Drosophila-Pellino antibody and the DFG for financial support.

[1] Resch et al. (1998) Mamm. Genome 9: 893-898. [2] Acampora et al. (1998) Development 125:1229-1239. [3] Grosshans et al. (1999) Mech Dev. 81:127-38.

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