| First Author | Sweet HO | Year | 1990 |
| Journal | Mouse Genome | Volume | 87 |
| Pages | 112 | Mgi Jnum | J:14294 |
| Mgi Id | MGI:62465 | Citation | Sweet HO, et al. (1990) Trembly-like (Tyl) - a new X-linked mutation in the mouse. Mouse Genome 87:112 |
| abstractText | Full text of Mouse Genome contribution: TREMBLY-LIKE (Tyl) - A NEW X-LINKED MUTATION IN THE MOUSE. H.O. Sweet, R.T. Bronson, B.S. Harris and M.T. Davisson; The Jackson Laboratory, Bar Harbor, ME 04609 U.S.A. INTRODUCTION We have identified a new sex-linked, semi-dominant, male lethal mutation that produces tremors, seizures, and paralysis before death. We present here preliminary characterization of the mutant and linkage data locating it on the X chromosome. MATERIALS AND METHODS The mutation arose in the B6A/FlJ hybrid colony in 1984. It is maintained in a balanced stock on the B6CBACa-Aw-J/A hybrid background using the X-linked marker tabby (Ta). Pathological analysis of the central nervous system was done on luxol fast blue stained sections. RESULTS Phenotype. Hemizygous Tyl/Y males exhibit a phenotype similar to jp/Y males. Tremors appear at 10 days followed by seizures, paralysis, and death prior to 20 days of age. Histologically Tyl/Y do not show the absence of myelin found in jimpy/Y. Some heterozygous Tyl/+ females can be identified at weaning. Tremors in these affected females are less severe than those seen in Tyl/Y. The Tyl/+ female tends to topple when walking because of rear leg incoordination. These females seldom have seizures nor do the rear legs become paralyzed, and life span is not affected. They are fertile and become increasingly kyphotic as they reach 8-10 months of age. Other Tyl/+ females can be identified as heterozygotes only by producing affected Tyl/Y progeny. Some of these tested females may develop neurological symptoms after having two or more litters while others remain phenotypically normal. Genetics. X-linkage was shown by breeding test (two Tyl/+ females x +/Y males produced 29 Tyl/Y sons, 28 +/Y sons, and 81 normal-appearing daughters). Two-point crosses with three X-linked genes, bent-tail (Bn), Ta, and X-linked polydactyly (Xpl) gave the following male progeny: Ta +/+ Tyl x + +/Y -> 90 Ta +, 70 + Tyl, 13 Ta Tyl, 14 + +, n = 186; Bn +/+ Tyl x + +/Y -> 30 Bn +, 24 + Tyl, 0 Bn Tyl, 0 + +, n = 54; Tyl +/+ Xpl -> 3 +Xpl, 5 Tyl +, 0 Tyl Xpl, 2 + +, n = 10. Three-point crosses are tabulated below. All Fl females were mated to B6CBAF1+ + + /Y males. Data are reported for male progeny only because females can not be scored unequivocally for Tyl. Fl female Parent: +TaXpl/Tyl+ +: + Ta Xpl: 10; Tyl + +: 5; Tyl Ta +: -; + + Xpl: 5; Tyl Ta Xpl: 1; + + +: 9; + Ta +: 3; Tyl + Xpl: 1; Total: 34. Fl female Parent: Tyl Ta +/+ + Xpl: Tyl Ta +: 12; + + Xpl: 11; Tyl + +: -; + Ta Xpl: -; Tyl Ta Xpl: 2; + + +: 2; + Ta +: 1; Tyl + Xpl: -; Total: 28. Fl female Parent: + Ta +/Tyl + Xpl: + Ta +: 4; Tyl + Xpl: 5; Tyl Ta Xpl: -; + + +: -; + Ta Xpl: 4; Tyl + +: 4; Tyl Ta +: 3; + + Xpl: 1; Total: 21. Fl female Parent: + Tyl Ta/Bn + + +: + Tyl Ta: 12; Bn + +: 11; Bn + Ta: -; Tyl + +: 3; Bn Tyl Ta: 1; + + +: 1; + + Ta: -; Bn Tyl +: 2; Total: 30. Because we were able to obtain only small numbers from each cross, we calculated the distances between Tyl and other loci by summing the data from all crosses: Tyl - Bn = 4/84 = 4.8 +/- 2.3; Tyl - Ta = 52/299 = 17.4 +/- 2.2; Tyl - Xpl = 33/93 = 35.5 +/- 5.0. The most likely order is [Bn, Tyl] - Ta -Xpl. A mating between a Tyl +/+ Ta female and a Bn/Y male produced an XXY male. At weaning age this individual displayed the neurological behavior seen in those Tyl/+ females identifiable at this age, a striped coat characteristic of Ta/+ females, a normal tail and clearly was a male. He was mated to a B6CBACa-Aw-J/A hybrid female but failed to produce progeny. He was sacrificed at four months of age and chromosomal analysis of bone marrow preparations confirmed he was XXY. DISCUSSION We describe a new mutant that has three abnormal phenotypes - tremors, seizures, and paralysis - usually each associated with individual genes. Tyl/Y males resemble trembly (Ty/+) males, which were reported to have tremors followed by seizures and death before weaning. Although both mutants have tremors like jp/Y mutants (1), neither has a demonstrable myelin deficiency. Tyl maps close to the position of Ty on the X chromosome. We can not rule out the possibility that Tyl is a remutation to Ty, because Ty is no longer available. Tyl/Y mutants may be useful for modeling human X-linked conditions with multiple neurological symptoms, such as the complicated spastic paraplegias (e.g., MIM Nos. 31289, 31290) (2). REFERENCES 1. Green, M.C. Catalog of mutant genes and polymorphic loci, p. 377. In: Genetic Variants and Strains of the Laboratory Mouse, 2nd Edition. M.F. Lyon and A.G. Searle, (eds.), Oxford University Press, 1989. 2. McKusick VA. Mendelian Inheritance in Man, 8th Ed. The Johns Hopkins University Press, Baltimore, 1988. |
