A Neurological Mutation on Mouse Chromosome 14 named agitans-like.
Patricia F. Ward- Bailey, Belinda S. Harris, Roderick T. Bronson and Muriel T. Davisson
Source of Support: This research was supported by grants NIH/NCRR RR01183 to the Mouse Mutant Resource (M.T. Davisson, P.I.) and Cancer Center Core Grant CA34196.
Mutation (allele) symbol: agil
Mutation (allele) name: agitans-like
Gene symbol: agil
Strain of origin: C3H/HeJ
Current strain name: C3H/HeJ-agil/GrsrJ
Stock #: 004780 (link to Jaxmice for purchase information)
Phenotype categories: neurological
Abstract
A neurological mutation named agitans-like has been found at The Jackson Laboratory. This autosomal recessive mutation is recognized by 15 days of age by its shaky, unsteady, wobbly gait. Mutants die around 3 weeks of age. This mutation maps to Chromosome 14 between D14Mit39 and D14Mit115which is near the neurological mouse mutation agitans (ag).
Origin and Description
This mutation was found in April 1999 in the strain C3H/HeJ at F233 by Faye Leonetti in a production colony at the Jackson Laboratory and brought to the Mouse Mutant Research (MMR) deviant search program. Homozygous mutants are easily recognized by 15 days of age by their wobbly gait and die about a week later. The strain is maintained by progeny testing.
Genetic Analysis
Tests for Allelism
A test for allelism with quaking (qk) produced 0 qk/16 born.
A test for allelism with wasted (wst) produced 0 wst/ 24born.
A test for allelism with shiverer (shi) produced 0 shi/33 born.
Tests for allelism were done with agil and three other phenotypically similar new mutants in the MMR and no mutants were produced.
A test for allelism with wabbler lethal (wl) which is listed as syntenic on Chr 14 is currently in progress.
Linkage Cross for Mapping
A heterozygous agil male was crossed to two female C57BL/6J mice and produced F1 progeny. Using our standard MMR procedures, these F1s were intercrossed to produce 72 F2 affected animals, of which 21 were used to determine the chromosomal location of the agitans-like mutation. A genome-wide scan using a DNA pool of 21 affected animals and parental controls indicated linkage on Chromosome 14 with D14Mit166. The individual DNAs from the linkage cross were then typed for this marker and 5 additional Chr 14 markers. The recombination estimates with standard errors and best gene order are: centromere-D14Mit5- 2.4 +/- 2.4-D14Mit39 - 2.4 +/-2.4-agil-2.4 +/- 2.4 - [D14Mit115, D14Mit225]-16.6 +/- 7.3 ? [D14Mit265, D14Mit166]. Gene order and recombination frequencies were calculated with the Map Manager computer program (Manley 1993). The complete Chr 14 linkage data for 21 F2 agil/agil mice has been deposited in the Mouse Genome Database, accession # J:85257. Based on the Ensembl assembly for Chr 14, the chromosomal position for agil is between 59213353 bp (D14Mit39) and 63304173 bp (D14Mit115). A neurological mutant named agitans (ag) has a very similar phenotype to this new mutation,and maps near the hairless locus (hr) which is located at 61014601-61032224 bp. Agitans-like may be a remutation to agitans, but a direct test for allelism was not done because the agitans strain is not available here at The Jackson Laboratory.
Pathology
A pathological screen of ten mutants and two controls, all at about 3 weeks of age, had slightly less deeply staining myelin in spinal cord stained with luxal fast blue. Three of ten mutants had a few scatttered dystrophic axons and degenerating myelin sheaths (myelin figures) in spinal cord white matter. These changes are consistant with early degeneration of spinal cord white matter. Hearing was assessed by ABR testing on three homozygous mutants and six +/- controls. The controls all had good hearing. The mutants varied from being deaf to showing moderate hearing loss. One of the homozygous mutants had little hearing with a long latency/central pathway problem as observed in the mutants shiverer and quaking.
Weight measurements were made on four 21-day old male mice. Two homozygous mutants appearing near death weighed 6.1 grams and 5.4 grams as compared to two littermate controls that weighed 10.1 grams and 10.6 grams.
Acknowledgements
The authors wish to thank Coleen Marden and Heping Yu for their technical expertise.
References
Mouse Genome Database (MGD) Mouse Genome Informatics Project, The Jackson Laboratory, Bar, Harbor, Maine. World Wide Web (URL: http://www.informatics.jax.org).
Manley KF (1993) A MacIntosh program for storage and analysis of experimental mapping data. Mamm Genome 4,303-313.
