The spontaneous mutation tippy causes Purkinje cell defects including abnormal dendrite formation and Purkinje cell degeneration. Homozygotes can be identified by 10 days of age by their smaller body size and difficulty in righting themselves. They can become hyperactive, cannot stand or walk without falling over, and die by 20 to 25 days of age.
Read More +Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Spontaneous | a | nonagouti |
Allele Type | Gene Symbol | Gene Name |
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Spontaneous | tip | tippy |
The spontaneous mutation tippy causes Purkinje cell defects including abnormal dendrite formation and Purkinje cell degeneration. Homozygotes can be identified by 10 days of age by their smaller body size and difficulty in righting themselves. They can become hyperactive, cannot stand or walk without falling over, and most die by 20 to 25 days of age. Only 25% of Purkinje cells display normal dendritic architecture. Most have abnormal dendritic branching, often having no clear secondary or tertiary dendritic branches. The Purkinje cells have many more spines located along the proximal dendritic shaft and the cell soma than are found in controls. Dendritic branches lack the normal self-avoidance and instead have meandering arbors, which overlap in their coverage, and dendritic spines are malformed, with thin, elongated filopodia. Aberrant Purkinje cell morphology is found throughout all lobules and across the vermis. At 18 days of age torpedos can be found at the initial Purkinje cell axon, and Purkinje cell degeneration is found, primarily in the anterior lobe and the banks of the secondary fissure, with damage in all compartments of the Purkinje neuron. There are more dystrophic axons in the cerebellar and vestibular nuclei than there are those undergoing advanced degeneration, and no vacuoles are observed in the Purkinje cell layer between 16 and 21 days of age. No Purkinje cell degeneration was found in the inferior olivary complex. Foliation and tri-laminar organization of the cerebellum are normal, but the cerebellum is smaller than normal. Granule, stellate, basket, golgi, Lugaro and unipolar brush border cells appear normal and correctly positioned, but there is upreglation of GFAP in Bergmann glia and astroglial cells of the granule layer, white matter and deep nuclei. (Shih et al., 2015 and Lane and Bronson, 1995.)
The tippy (tip) mutation arose spontaneously in 1977 at The Jackson Laboratory in the progeny of a B6C3Fe a/a-Csf1op/+ female and a Tbx15de-H homozygous male. The tip mutation was bred away from the other mutation through four crosses to B6C3Fe-a/a and then maintained by ovarian transplant cross-intercross using B6C3Fe-a/a for the cross. In 1991 heterozygotes at approximately generation N20 were intercrossed to generate embryos for cryopreservation and in 1995 heterozygotes at approximately generation N31 were intercrossed to generate more embryos for cryopreservation.
Allele Name | nonagouti |
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Allele Type | Spontaneous |
Allele Synonym(s) | |
Gene Symbol and Name | a, nonagouti |
Gene Synonym(s) | |
Strain of Origin | old mutant of the mouse fancy |
Chromosome | 2 |
General Note | Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039 |
Molecular Note | Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for at-2Gso and Aw-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type. |
When using the tippy mouse strain in a publication, please cite the originating article(s) and include JAX stock #001055 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Homozygous, Heterozygous or wildtype for tip, 1 pair minimum |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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