Table 1.

Nebulin animal models

Animal model	Description	Phenotype	Background	Publication
Neb KO mouse	Deletion of exon 1 (replacement with Cre recombinase, neomycin and frt) No nebulin expression	Mice die within 8–11 days after birth from muscle weakness, normal sarcomere assembly, 25% shorter thin filaments and reduced force	C57/BE and Black Swiss	Bang et al. (2006)
Neb+/− Rosa 26 mice	Β-galactosidase expression in tissues expressing nebulin	Viable and indistinguishable from wild-type litter mates	C57/B6 and Black Swiss Rosa26	Bang et al. (2006)
Neb KO mouse	Deletion of Cap site, TATA-box and amino-terminus of nebulin resulting in complete absence of nebulin protein	Growth retardation and severe myopathy. ~ 90% of mice die within the first 2 weeks and the remaining animals die in week 3	N/D	Witt et al. (2006)
neb mutant Zebrafish	Point mutation in nebulin IVS43+1G>A, a mutation in the canonical splice donor site abolishes splicing of exon 43 and results in skipping of exon 43 (ENSDART00000061293) No protein expression or protein without N-terminus Exon 43 is the equivalent of exon 78 in human NEB (nemaline myopathy patients with mutations in this exon were previously reported)	Progressive loss of motor function, fish die within 5–7 days post fertilisation	N/D	Telfer et al. (2012) generated by ENU mutagenesis at the Sanger Institute Zebrafish Mutant Resource
Neb ΔExon55 mouse	In frame deletion of exon 55 to model a founder mutation frequently observed in nemaline myopathy patients, results in severely reduced protein levels of nebulin (~ 2% on post-natal day 5)	Growth retardation and death within 1 week after birth	C57/B6J	Ottenheijm et al. (2013)
Neb ΔSH3 mouse	Knock in of a stop codon at the 3′ end of the nebulin serine-rich region (residue I7097, exon 166 encoded by the last exon of nebulin). Truncated nebulin was expressed at levels comparable to wild type	No histological or ultrastructural abnormalities, normal isometric stress, but more vulnerable to eccentric contraction induced injury	C57/BL6	Yamamoto et al. (2013)
Neb conditional KO (cKO) mouse	The translational start codon of the Neb gene was knock out using the flox-Cre system under the control of the muscle creatine kinase promotor. This results in nebulin protein expression reduction to hardly detectable levels in striated muscle within weeks after birth	50% of mice die within 3 months, most remaining mice survive to adulthood. They display lower body weight, contractile defects, nemaline rods, switch to oxidative fiber type	N/D	Li et al. (2015)
neb mutant zebrafish strain sa906	Nonsense mutation in neb exon 30 (of 134)	Reduced swim performance, nemaline bodies and actin accumulations, reduced muscle mass and reduced sarcomeric organisation		Sztal et al. (2018)
neb mutant zebrafish strain sa906/Lifeact-eGFP	Nonsense mutation in neb exon 30 (of 134); crossed with Tg (Lifeact-eGFP) transgenic line	Reduced swim performance, nemaline bodies and actin accumulations, reduced muscle mass and reduced sarcomeric organisation; actin in all thin filaments labelled		Sztal et al. (2018)
NebΔ163–165	Stop codons after the start of murine exon 163; complete translation of the final actin-binding module M206, lacking serine rich region and SH3 domain. Resulted in a reduction in nebulin levels in EDL, normal protein levels in SOL	Initial high mortality (within the first week) as judged from a skewed Mendelian ratio. 87% of surviving homozygous mice survived to adulthood Reduced body weight which was due to loss of muscle mass rather than reduced growth (tibia length was unchanged)	C57BL/6J	Li et al. (2019)