Tub-KO Mice

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Catalog Number: C001386

Strain Name: C57BL/6JCya-Tubem1/Cya

Genetic Background: C57BL/6JCya

Reproduction: Homozygote x Homozygote


Strain Description

The TUB bipartite transcription factor (TUB) gene encodes a member of the Tubby family of proteins that play a role in obesity and sensory degeneration. The four members of the Tubby protein family in vertebrates share similar structural domains, including a highly conserved C-terminal domain that mediates DNA binding and a divergent N-terminal region containing nuclear localization signals and transcriptional activation structural domains, which are associated with interprotein binding[1].

TUB can function by binding to the intraciliary transport A protein (IFTAP) in the eye, and similar to other members of the Tubby family, TUB is also involved in controlling the initiation of phagocytosis and facilitating the clearance of apoptotic cells or cellular debris by retinal pigment epithelial cells (RPE) and macrophages. Diseases associated with TUB mutations and functional abnormalities include retinal dystrophy (RD), retinitis pigmentosa (RP), and obesity[2-3]. Mice carrying a spontaneous mutation in the Tub gene (Tubby mice) present a phenotype of obesity at maturity, retinal degeneration, and progressive hearing loss, and the phenotype in this mouse is associated with a deficiency in Tub protein function due to abnormal splicing of the Tub gene[4].

This strain is a mouse Tub knockout model that uses gene editing technology to knock out the homolog of the human TUB gene in mice. The Tub knockout mouse model has been reported to have the same phenotype as Tubby mice carrying spontaneous mutations in the Tub gene, and the deletion of Tub gene expression in mice leads to abnormalities of photoreceptors in the retina through apoptosis, which subsequently causes defects in the retina[5], and this model can be used for the study of retinal degeneration and related diseases.

 

The mouse Tub gene is located on chromosome 7, and exon 2-11 of this gene was knocked out using gene editing techniques.

● Retinal Degeneration (RD) Research;

● Obesity Mechanism Research;

● Other Retinal and Hearing Diseases Research.

1. Electroretinogram (ERG) testing

Figure 1. Electroretinogram (ERG) detection results of WT and 6-week-old Tub-KO mice. The amplitudes of both a- and b-waves in the scotopic and photopic ERGs of 6-week-old Tub-KO mice were lower than those of WT mice, indicating an impairment in light perception in the eyes of Tub-KO mice. Tub-KO mice have an early onset mild retinal degeneration.

 

2. Fundus morphology and optical coherence tomography (OCT) of the retina

Figure 2. Fundus morphology and OCT results of WT and 6-week-old Tub-KO mice. Compared with WT, Tub-KO mice showed abnormal retinal morphology with a mildly granular appearance. Tub-KO mice have an early onset mild retinal degeneration.

 

Retinal pathological evaluation of Tub-KO mice and wild-type mice by electroretinography (ERG) and optical coherence tomography (OCT) showed that the retinal fundus of Tub-KO mice showed a mildly granular appearance and reduced ERG waveform amplitude compared to wild-type mice, indicating a retinal disorder in this model.

In conclusion, the Tub-KO mice are a model of retinal degeneration that can be used in subsequent studies of retinitis pigmentosa (RP) and other retinal diseases as well as obesity or hearing loss, providing a useful tool for the study of human disease.

 

References

[1] Boggon TJ, Shan WS, Santagata S, Myers SC, Shapiro L. Implication of tubby proteins as transcription factors by structure-based functional analysis. Science. 1999 Dec 10;286(5447):2119-25.
[2] Ziccardi L, Niceta M, Stellacci E, Ciolfi A, Tatti M, Bruselles A, Mancini C, Barbano L, Cecchetti S, Costanzo E, Cappa M, Parravano M, Varano M, Tartaglia M, Cordeddu V. Biallelic Inactivating TUB Variants Cause Retinal Ciliopathy Impairing Biogenesis and the Structure of the Primary Cilium. Int J Mol Sci. 2022 Nov 24;23(23):14656.
[3] Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006 Nov 18;368(9549):1795-809.
[4] Coleman DL, Eicher EM. Fat (fat) and tubby (tub): two autosomal recessive mutations causing obesity syndromes in the mouse. J Hered. 1990 Nov-Dec;81(6):424-7.
[5] Stubdal H, Lynch CA, Moriarty A, Fang Q, Chickering T, Deeds JD, Fairchild-Huntress V, Charlat O, Dunmore JH, Kleyn P, Huszar D, Kapeller R. Targeted deletion of the tub mouse obesity gene reveals that tubby is a loss-of-function mutation. Mol Cell Biol. 2000 Feb;20(3):878-82.