A full-length human TAR DNA binding protein (TARDBP or TDP-43) cDNA sequence was modified to have both an N-terminal myc tag and the glutamine to lysine substitution at amino acid 331 associated with familial ALS (huTDP-43*Q331K). This huTDP-43*Q331K cDNA sequence was inserted between exon 2 and exon 3 of mouse prion protein (PrP or Prnp) gene at two unique XhoI sites in the MoPrP.XhoI plasmid vector (ATCC#JHU-2). The resulting MoPrP.XhoI-^mychuTDP-43*Q331K transgene was flanked with loxP sites, and then injected into the pronuclei of fertilized C57BL6/C3H hybrid eggs, which were implanted into pseudopregnant female mice. Transgenic founder mice were bred to C57BL/6 mice, and founder line 103 was identified with ~2.5-fold greater total TDP-43 (~1.5-fold greater huTDP-43*Q331K) expression levels in spinal cord as compared to endogenous TDP-43 in non-transgenic mice. These Prp-TDP-43^Q331K [~1.5x] transgenic mice were bred with C57BL/6NCrl females for at least nine generations prior to sending to The Jackson Laboratory in 2012 (see SNP note below). Upon arrival, transgenic mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish The Jackson Laboratory colony.

From this strain's arrival in 2012 through 2016, our 32 SNP (single nucleotide polymorphism) panel, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the Stock No. 017933 rederived living colony at The Jackson Laboratory. As expected, this showed all SNPs as C57BL/6 genetic background with all C57BL/6 substrain markers as C57BL/6N allele-type.
Beginning in 2017 to present (2021), The Jackson Laboratory has employed an expanded 48 SNP panel that includes several new markers. These results again showed all markers as C57BL/6 allele-type. In addition, all C57BL/6 substrain markers were C57BL/6N allele-type with one exception - the new marker on chromosome 6 [~107.8 Mbp] shows some C57BL/6N or C57BL/6J allele-type. Importantly, this new chromosome 6 SNP has previously shown that C57BL/6NCrl allele-type is the same as C57BL/6J allele-type (rather than C57BL/6NJ allele-type). Taken together, this strongly suggests that the live colony of Stock No. 017933 is a mix of C57BL/6NJ;C57BL/6NCrl.

• Noncarrier

Approximate Controls

• 005304 C57BL/6NJ

Additional Information

• Considerations for Choosing Controls

• Arnold ES; Ling SC; Huelga SC; Lagier-Tourenne C; Polymenidou M; Ditsworth D; Kordasiewicz HB; McAlonis-Downes M; Platoshyn O; Parone PA; Da Cruz S; Clutario KM; Swing D; Tessarollo L; Marsala M; Shaw CE; Yeo GW; Cleveland DW. 2013. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43. Proc Natl Acad Sci U S A 110(8):E736-45PubMed: 23382207MGI: J:191785