STOCK Ts(17¹⁶)66Yah/J

Stock number: 036600
Product name: Ts66Yah
Research areas: Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

This strain ships with remnant UID MiniMax microchips implanted subcutaneously in the back. For more information on these RFID chips, including our FAQ, please visit our Mouse Identification page.

Ts66Yah mice are trisomic for about two-thirds of the genes orthologous to human chromosome 21, but lack the non-homologous 6.2Mb 17¹⁶ minichromosomal segment. These mice may be used for studying Down Syndrome.

Detailed description

The trisomic Ts(17¹⁶)65Dn mouse models (Stock No. 001924 and Stock No. 005252) have been useful models for studying Down syndrome. Ts65Dn mice have three copies of most of the genes on mouse Chr 16 that are orthologous to human Chr 21 (Hsa21) genes. These extra genes, along with the centromere and about 5% of proximal mouse Chr 17 are contained in a small extra chromosome ("minichromosome"), and derived from a reciprocal translocation. The Ts65Dn trisomic minichromosome also contains a region that is non-homologous to Hsa21, (Pisd-ps2/Scaf8 to Pde10a), which contains 46 protein-coding genes. Using CRISPR/Cas9 technology, the donating laboratory has deleted the 6.2Mb region (Pisd-ps2/Scaf8 to Pde10a) of the 17¹⁶ minichromosome yielding a new trisomic model, Ts66Yah.

Ts66Yah trisomy mice demonstrate a similar behavioral phenotype to Ts65Dn mice for nesting, object recognition and spontaneous alternation tests. However, these Ts66Yah mice do not display the anxiety and hyperactivity phenotypes apparent in the original Ts65Dn models. While significant brain and craniofacial morphologies were measured in Ts66Yah mice compared to wildtype littermates, there were also subtle differences between Ts66Yah mice and Ts65Dn mice. It was found that theTs65Dn brain was larger than the Ts66Yah brain in many different regions and more severe brachycephaly noted in Ts66Yah mice resulting in increased mid-face shortening. [Duchon et al., Dis Model Mech. 2022 15:dmm049721].

The donating laboratory has indicated that the Ts66Yah female mice are fertile. Most male mice are also fertile, with 31 of 49 males tested as fertile by the donating investigator. However, male fertility should be monitored closely over generations. The donating laboratory maintained the Ts66Yah mice on a B6C3BF1 (C57BL/6 x C3B) background. The C3B mice are a sighted C3H/HeN congenic line for the BALB/c allele at the phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide (Pde6b) locus (Hart et al, Invest Ophthalmol Vis Sci.(2005)).

Please see the Down Syndrome and Cytogenetics Models Resource for more information.

Please note, at The Jackson Laboratory, Stock No. 036600 is maintained by breeding to B6EiC3Sn.BLiAF1/J (Stock No. 003647) and is therefore segregating for the Clcc1^m1J spontaneous mutation. See additional details below.
In 2015, researchers at The Jackson Laboratory discovered C3H/HeSnJ inbred mice harbor a spontaneous, intracisternal A-particle (IAP) retrotransposon-mediated insertion in exon 2 of Clcc1 locus (Clcc1^m1J) resulting in a loss of function mutation. CLCC1 is an endoplasmic reticulum-resident chloride channel. Mice homozygous for Clcc1^m1J exhibit ataxia, muscle wasting and cerebellar neurodegeneration later in life (11-12 months). For more information, please review this article: Jia et al. 2015 J Neurosci 35:3001 [PMID:25698737].

Development

Dr. Yann Herault obtained some Ts65Dn mice (Stock No. 001924). The Ts65Dn trisomic mouse harbors a reciprocal translocation T(16C3-4;17A2)65Dn that includes 90 protein-coding genes (Mir155 to Zbtb21) on mouse chromosome 16 (Mmu16), which are homologous to human chromosome 21 (Hsa21), translocated to the centromeric part of mouse chromosome 17 (Mmu17). This minichromosome also contains a region that is non-homologous to Hsa21 (Pisd-ps2/Scaf8 to Pde10a) which contains 46 protein-coding genes.

Using CRISPR/Cas9 technology, the Herault laboratory deleted the 6.2Mb region (Pisd-ps2/Scaf8 to Pde10a) of the 17¹⁶ minichromosome yielding a new trisomic model, Ts66Yah. Two pairs of guide RNAs targeting the centromeric region of Mmu17 (GRCm39 17:3121550-3122030, at 43 kb from Scaf8) and 3' breakpoint of the minichromosome on Mmu16 (Mmu16:84151598-84152123, at 363 kb from Mrpl39) and Cas9 nuclease were introduced into the pronuclei of fertilized oocytes obtained after in vitro fertilization of B6C3BF1 females with the sperm of a Ts65Dn fertile male. A single founder male was identified by junction PCR and bred to C57BL/6NCrl females. The resulting mice were then maintained on a B6C3BF1 background by the donating laboratory prior to sending fertile males to The Jackson Laboratory. Upon arrival, their sperm was used to fertilize B6EiC3Sn.BLiAF1/J oocytes (Stock No. 003647). Thereafter, we will maintain our live colony by breeding carrier Ts66Yah females with B6EiC3Sn.BLiAF1/J (Stock No. 003647) males.

Allele

Symbol: Ts(17¹⁶)66Yah
Name: trisomy, Chr 16 translocation to Chr 17, Yann Herault 66
MGI accession ID: MGI:6459295
Generation method: Endonuclease-mediated
Attributes: Inserted expressed sequence
Synonyms: Ts66Yah
Marker symbol: Ts(17¹⁶)66Yah
Marker name: trisomy, Chr 16 translocation to Chr 17, Yann Herault 66
Chromosome: 17
Strain of origin: B6EiC3Sn a/A-Ts(17¹⁶)65Dn/J
Molecular note: CRISPR targeting removed a 6 Mb segment from the centromeric region of the Mmu17 chromosome of the original translocation, encompassing many genes not homologous to Hsa21.