Journal: bioRxiv

Article Title: Mysm1 mutations in meander tail mice cause anterior-selective cerebellum malformation

doi: 10.64898/2026.02.25.708017

Figure Lengend Snippet: ( A ) Genetic crosses localized mea alleles on chromosome 4. Regions definitively excluded by heterozygosity in an affected animal shown as black bars. Recombinants whose interpretation relied on penetrance in an unaffected animal are shown in grey. ( B ) PacBio HiFi reads identified a Y34X variant in mea J not present in its BKS.Cg parental strain control. ( C ) AlphaFold2 model of mouse MYSM1 shows position of the Y34X nonsense variant and the next in-frame methionine at residue 65. ( D ) Small patches of abdominal white spotting were seen on most BKS.Cg– mea J homozygotes. (E) Sanger sequencing of Mysm1 exons identified a R659G missense variant in mea 2J . (F) AlphaFold2 model shows position of the R659G variant on the surface of the catalytic MPN domain. (G) Larger patches of white spotting were typical of BKS.Cg– mea 2J homozygotes.

Article Snippet: BKS.Cg– Dock7 m + / + Lepr db (Stock #000700), BKS.Cg– mea J Lepr db / + + (Stock #001192), and BKS.Cg– mea 2J Dock7 m / + + (Stock #001049) were obtained from live colonies and cryopreserved stocks at The Jackson Laboratories, as were mapping partner strains CAST/EiJ (Stock #000928), A/J (Stock #000646), and FVB/NJ (Stock #001800).

Techniques: Variant Assay, Control, Residue, Sequencing

Journal: bioRxiv

Article Title: Mysm1 mutations in meander tail mice cause anterior-selective cerebellum malformation

doi: 10.64898/2026.02.25.708017

Figure Lengend Snippet: ( A ) Reference (Ref) and 23-bp deletion allele (D32Efs) recovered at exon 2. RNA guide sequence is underlined, with protospacer-adjacent motif shaded. Arrowhead, predicted cleavage site. Lowercase intron, uppercase exon sequences. Asterisk, T>A in mea J . ( B ) Compound mea J /Δ96 heterozygotes had shorter, kinked tails with variegated pigmentation characteristic of mea . ( C ) Classical mea alleles (from stocks carrying closely-linked Lepr db or Dock7 m mutation) and compound heterozygotes between mea J and either mea 2J or D32Efs all showed reductions in white blood cells (WBC), neutrophils (NE), lymphocytes (LY), and red blood cells (RBC), but elevated mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), consistent with the bone marrow failure reported for Mysm1 knockout mice. Mutants in orange, sex-matched littermate controls navy. ( D ) Midline sagittal images illustrate selective reduction of the anterior compartment (folia I-VIa, grey mask) in mea 2J , D32Efs, and compound heterozygous mutations relative to littermate controls. ( E ) Measured areas at midline showed dramatic reductions of the anterior and slight reductions in the posterior cerebellum relative to sex-matched littermates in both females (orange) and males (cyan).

Article Snippet: BKS.Cg– Dock7 m + / + Lepr db (Stock #000700), BKS.Cg– mea J Lepr db / + + (Stock #001192), and BKS.Cg– mea 2J Dock7 m / + + (Stock #001049) were obtained from live colonies and cryopreserved stocks at The Jackson Laboratories, as were mapping partner strains CAST/EiJ (Stock #000928), A/J (Stock #000646), and FVB/NJ (Stock #001800).

Techniques: Sequencing, Mutagenesis, Knock-Out

Journal: bioRxiv

Article Title: Mysm1 mutations in meander tail mice cause anterior-selective cerebellum malformation

doi: 10.64898/2026.02.25.708017

Figure Lengend Snippet: ( A ) Amino acid sequence for mouse reference, Y34X ( mea J ), and D32Efs*13 (Δ23) alleles, showing deleted (-), termination (*), and next available in-frame AUG (M65) codons. ( B ) Comparable human reference and ClinVar alleles W51X and D92Efs relative to potential reinitiation codons at M68, M97, and M107. ( C ) Western blots of E17.5 mouse brains from control (+/+) and mutant (mut) littermate pairs for each of the three Mysm1/mea mutations using rabbit anti-MYSM1 antibody. Arrow, wild-type protein size. ( D ) Loading control on the same membrane using mouse anti-TUBG. ( E ) Dual luciferase assays using aminoterminal fusions of the fragments shown in (A) for both mouse and human MYSM1 variants plotted as log2 of the ratio of Nano luciferase to firefly luciferase. Colors denote two to three replicate transfections for each of four independent plasmid preparations. Vertical line, median of three negative controls with a frameshifted Nano luciferase.

Article Snippet: BKS.Cg– Dock7 m + / + Lepr db (Stock #000700), BKS.Cg– mea J Lepr db / + + (Stock #001192), and BKS.Cg– mea 2J Dock7 m / + + (Stock #001049) were obtained from live colonies and cryopreserved stocks at The Jackson Laboratories, as were mapping partner strains CAST/EiJ (Stock #000928), A/J (Stock #000646), and FVB/NJ (Stock #001800).

Techniques: Sequencing, Western Blot, Control, Mutagenesis, Membrane, Luciferase, Transfection, Plasmid Preparation