Ataxia and a cerebellar defect in the exencephaly-prone SELH/Bc mouse stock.
SELH/Bc inbred mice have an abnormal mechanism of anterior neural tube closure and 10-20% of embryos have a lethal neural tube closure defect, exencephaly. Our previous studies have focused on this multifactorial threshold trait. However, SELH mice are also characterized by another trait that also shows non-Mendelian transmission ratios, an ataxia recognized in juvenile and adult mice. Here we report our first genetic and morphological studies of the ataxia trait. Recent pedigree records for the SELH colony showed that 7% of the 467 weaned progeny from normal breeding pairs were ataxic; 17 of the 20 pairs produced ataxic progeny. This result was statistically consistent with the hypothesis that all SELH mice have the ataxic genotype, which is expressed in only 7% of them. Genetic studies of an outcross to a normal strain and the subsequent F2 and testcross of the F2 were also done. The results were consistent with a one or two gene locus cause of liability to ataxia in SELH mice. The genetic correlation between exencephaly production and ataxia production for a sample of nine F2 males was 0.35, as expected if both traits are caused by the same genes, but was not statistically significant. In another approach, we examined the morphology of brains from normal and ataxic adult SELH mice. All 20 brains from non-ataxic SELH mice were morphologically normal. In all 18 brains from ataxic SELH mice the cerebellum was abnormal, lacking the vermis, and characterized by a midline fissure. This phenotype in mice has previously been known in Mendelian mutants at the Wnt-1 locus.(ABSTRACT TRUNCATED AT 250 WORDS)
Juriloff
D M
DM
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Harris
M J
MJ
Harrod
M L
ML
Gunn
T M
TM
Miller
J E
JE
D000818:Animals; D002524:Cerebellar Ataxia / Q000235:genetics* / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains / Q000196:embryology* / Q000235:genetics; D009436:Neural Tube Defects / Q000235:genetics*; D010641:Phenotype