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. 2021 Jun 4;24(7):102684. doi: 10.1016/j.isci.2021.102684

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© 2021 The Authors

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Generation of tuberous sclerosis reporter mouse model

(A) Schematic of genetic crosses to generate Tsc2^+/− reporter mouse models shows floxed R26Sor^{tm9(CAG-tdTomato)Hze} mice (female, N = 10 animals) were crossed with Tg(Mpz-Cre)26Mes mice (male, N = 10 animals) expressing Cre recombinase under the control of myelin protein zero (Mpz) promoter. Mice with Mpz(Cre)^tm1.1JDar mouse progeny (male/female, N = 8 animals) were then mated with Tsc2^+/− mice (male/female, N = 10 animals) to source Tsc2^+/−/Mpz(Cre)/TdT^fl/fl tuberous sclerosis reporter mouse models (shown in red) (male/female, N = 24 animals) that spontaneously develop renal tumors driven by neural crest cells labeled with tdTomato.

(B) IVIS spectral images of abdominopelvic cavities of 1.3-yr-old Tsc2^+/−/Mpz(Cre)/TdT^fl/fl tuberous sclerosis mouse model compared to age-matched Tsc2^+/-Mpz(Cre)TdT^+/+ and Tsc2^+/+Mpz(Cre)TdT^fl/fl mice distinguishing epifluorescence of tdTomato-expressing regions.

(C) Average radiant efficiency was used to compare tdTomato epifluorescence in these mouse models by one-way analysis of variance (ANOVA) and post-hoc Dunnett's test (p < 0.0001∗∗∗∗). Small animal ultrasound scans of sagittal sections of normal kidney (NK) parenchyma in adult wild-type mice imaged on a viewing stage in supine position (D1) in comparison to renal sagittal sections in Tsc2^+/-Mpz(Cre)TdT^fl/fl mice (D2) with labeled sites of tumors (T). BV denotes blood vessels. Rapid magnetic resonance images of kidneys (E) in Tsc2^+/-Mpz(Cre)TdT^fl/fl mice identifying tumors (T) shown with arrows. See also Figures S1A–S1C comparing ultrasound and MRI images of tumorigenic hepatic tissues in Tsc2^+/-Mpz(Cre)/TdT^fl/fl mice to normal liver tissue of Tsc2^+/+Mpz(Cre)/TdT^fl/fl mice.