Csn1s1-KO Mouse

Csn1s1, encoding αS1-casein, is one of the genes responsible for encoding milk protein fractions, along with CSN1S2, CSN2 and CSN3. Caseins play an evolutionarily conserved role in nutrition [5]. The regulation of Csn1s1 can potentially influence milk composition, which is of great significance in livestock breeding [5].

In research, a hypomorphic mutation in the mouse Csn1s1 gene generated by CRISPR/Cas9 pronuclear microinjection showed a 50 % reduction in gene expression and a 40-80 % decrease in Csn1s1 protein amount, negatively affecting milk composition [5]. In goats, overexpressing CSN1S1 decreased β-casein (CSN2) mRNA and protein abundance, while interference of CSN1S1 led to a significant increase in β-casein abundance, suggesting CSN1S1 inhibits β-casein synthesis via the JAK2/STAT5a signaling pathway [4]. In cows, in the second lactation, cows with the BB genotype of CSN1S1 had significantly higher milk, protein, and fat yields than those with BC genotype [2]. In buffaloes, an SNP was found in the promoter region of the CSN1S1 gene [1]. In Sahiwal cattle, two SNPs at CSN1S1 gene were associated with dry-period, and one SNP was associated with average calving-interval [3].

In conclusion, Csn1s1 is crucial for milk protein composition and production in livestock. Mouse models with Csn1s1 gene mutations have revealed its role in milk composition. Understanding Csn1s1 can potentially assist in genetic selection in livestock breeding, and its study also provides insights into the regulation mechanism of milk protein synthesis.

References:

1. Medeiros, Natalia B C, Guerreiro, Sávio L M, Pereira, Rairiana S R, Hamoy, Igor G, Rodrigues, Marília D N. 2022. CSN1S1 and CSN3 gene variants in female Murrah buffaloes in the Brazilian Amazon. In Anais da Academia Brasileira de Ciencias, 94, e20211394. doi:10.1590/0001-3765202220211394. https://pubmed.ncbi.nlm.nih.gov/36197363/

2. Čítek, Jindřich, Samková, Eva, Brzáková, Michaela, Hasoňová, Lucie, Hálová, Karolína. 2023. CSN1S1 and LALBA Polymorphisms and Other Factors Influencing Yield, Composition, Somatic Cell Score, and Technological Properties of Cow's Milk. In Animals : an open access journal from MDPI, 13, . doi:10.3390/ani13132079. https://pubmed.ncbi.nlm.nih.gov/37443877/

3. Asim, Muhammad, Saif-Ur Rehman, Muhammad, Hassan, Faiz-Ul, Awan, Faisal Saeed. 2022. Genetic variants of CSN1S1, CSN2, CSN3, and BLG genes and their association with dairy production traits in Sahiwal cattle and Nili-Ravi buffaloes. In Animal biotechnology, 34, 2951-2962. doi:10.1080/10495398.2022.2126365. https://pubmed.ncbi.nlm.nih.gov/36165734/

4. Song, Ning, Chen, Yating, Luo, Jun, Li, Cong, Loor, Juan J. 2020. Negative regulation of αS1-casein (CSN1S1) improves β-casein content and reduces allergy potential in goat milk. In Journal of dairy science, 103, 9561-9572. doi:10.3168/jds.2020-18595. https://pubmed.ncbi.nlm.nih.gov/32828499/

5. Smirnov, A V, Shnaider, T А, Korablev, A N, Serova, I A, Battulin, N R. . A hypomorphic mutation in the mouse Csn1s1 gene generated by CRISPR/Cas9 pronuclear microinjection. In Vavilovskii zhurnal genetiki i selektsii, 25, 331-336. doi:10.18699/VJ21.036. https://pubmed.ncbi.nlm.nih.gov/34901729/