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RESEARCH ARTICLE

Investigation of myostatin and calpain 3 gene polymorphisms and their association with milk-production traits in Sfakia sheep

Adel H. M. Ibrahim A D , Nikolaos Tzanidakis B , Smaragda Sotiraki B , Huitong Zhou C and Jonathan Hickford C
+ Author Affiliations
- Author Affiliations

A Department of Animal Breeding, Desert Research Center, 1 Matehaf AlMatariya Street, AlMatariya, Cairo 11753, Egypt.

B Veterinary Research Institute, Hellenic Agriculture Organisation, Thermi, TK 57001, Thessaloniki, Greece.

C Gene-Marker Laboratory, Department of Agricultural Sciences, Lincoln University, POB 84, Lincoln 7647, New Zealand.

D Corresponding author. Email: adelhosseiny2005@yahoo.com

Animal Production Science 60(3) 347-355 https://doi.org/10.1071/AN18799
Submitted: 16 January 2019  Accepted: 28 June 2019   Published: 3 December 2019

Abstract

Context: Genetic selection based on genetic markers for economically important traits in Sfakia sheep.

Aims: The aim of the present study was to investigate variation in the ovine myostatin gene (MSTN) and calpain 3 gene (CAPN3), and their association with milk-production traits.

Methods: Records for milk yield, milk fat content, protein content, lactose content, and non-fat solid content, pH and somatic-cell score (log), were obtained from 376 Sfakia ewes. Polymerase chain reaction–single-strand conformational polymorphism (PCR–SSCP) analyses were used to detect variation in intron 1 of MSTN and exon 10 of CAPN3. General linear models were then used to test for associations between the variation in MSTN and CAPN3, and milk-production traits.

Key results: The SSCP banding patterns for MSTN showed four variants (A1, A2, A3 and A4), which contained nine nucleotide sequence differences. Four SSCP banding patterns (C1, C2, C3 and C4) were observed for CAPN3 and these contained eight nucleotide-sequence differences. The MSTN variation was associated (P < 0.05) with variation in milk yield and non-fat milk solid content. Variation in CAPN3 was associated with milk yield (P < 0.001), fat content (P < 0.05) and lactose content (P < 0.05). Association analyses between the presence/absence of MSTN and CAPN3 variants and milk-production traits showed that a variant of MSTN that had previously between associated with muscle hypertrophy was associated with decreased milk yield (P < 0.05) and a lower non-fat milk solid content (P < 0.01). A CAPN3 variant that had previously been associated with increased sheep-carcass loin lean-meat yield was associated with a decreased milk yield (P < 0.01) and a decreased milk fat content (P < 0.05).

Conclusions: Our results have provided an insight into the effects of variation in ovine MSTN and CAPN3 on milk-production traits in sheep.

Implications: To preserve the dual-purpose characteristics of Sfakia sheep, breeding goals should take into account the possible antagonism between meat and milk traits.

Additional keywords: CAPN3, milk traits, MSTN.


References

Beckmann JS, Spencer M (2008) Calpain 3, the ‘gatekeeper’ of proper sarcomere assembly, turnover and maintenance. Neuromuscular Disorders 18, 913–921.
Calpain 3, the ‘gatekeeper’ of proper sarcomere assembly, turnover and maintenance.Crossref | GoogleScholarGoogle Scholar | 18974005PubMed |

Berry DP, Friggens NC, Lucy M, Roche JR (2016) Milk production and fertility in cattle. Annual Review of Animal Biosciences 4, 269–290.
Milk production and fertility in cattle.Crossref | GoogleScholarGoogle Scholar | 26526546PubMed |

Buske B, Gengler N, Soyeurt H (2011a) Short-communication: influence of the muscle hypertrophy mutation of the myostatin gene on milk production traits and milk fatty acid composition in dual-purpose Belgian Blue dairy cattle. Journal of Dairy Science 94, 3687–3692.
Short-communication: influence of the muscle hypertrophy mutation of the myostatin gene on milk production traits and milk fatty acid composition in dual-purpose Belgian Blue dairy cattle.Crossref | GoogleScholarGoogle Scholar | 21700058PubMed |

Buske B, Szydlowski M, Verkenne C, Gengler N (2011b) Estimating myostatin gene effect on milk performance traits using estimated gene content for a large number of non-genotyped cows. Animal 5, 43–47.
Estimating myostatin gene effect on milk performance traits using estimated gene content for a large number of non-genotyped cows.Crossref | GoogleScholarGoogle Scholar | 22440700PubMed |

Byun SO, Fang Q, Zhou H, Hickford JG (2009) An effective method for silver-staining DNA in large numbers of polyacrylamide gels. Analytical Biochemistry 385, 174–175.
An effective method for silver-staining DNA in large numbers of polyacrylamide gels.Crossref | GoogleScholarGoogle Scholar | 19013423PubMed |

Cannas A (2002) Feeding of lactating ewes. In ‘Dairy sheep feeding and nutrition’. (Ed. G Pulina) pp. 123–166. (Avenue Media: Bologna, Italy)

Carrarelli P, Yen CF, Arcuri F, Funghi L, Tosti C, Wang TH (2015) Myostatin, follistatin and activin Type II receptors are highly expressed in adenomyosis. Fertility and Sterility 104, 744–752.e1.
Myostatin, follistatin and activin Type II receptors are highly expressed in adenomyosis.Crossref | GoogleScholarGoogle Scholar | 26086422PubMed |

Dai W, Wang Q, Zhao F, Liu J, Liu H (2018) Understanding the regulatory mechanisms of milk production using integrative transcriptomic and proteomic analyses: improving inefficient utilization of crop byproducts as forage in dairy industry. BMC Genomics 19, 403
Understanding the regulatory mechanisms of milk production using integrative transcriptomic and proteomic analyses: improving inefficient utilization of crop byproducts as forage in dairy industry.Crossref | GoogleScholarGoogle Scholar | 29843597PubMed |

de Rancourt M, Fois N, Lavin MP, Tchakerian E, Vallerand F (2006) Mediterranean sheep and goats production: an uncertain future. Small Ruminant Research 62, 167–179.
Mediterranean sheep and goats production: an uncertain future.Crossref | GoogleScholarGoogle Scholar |

de Vries MJ, Veerkamp RF (2000) Energy balance of dairy cattle in relation to milk production variables and fertility. Journal of Dairy Science 83, 62–69.
Energy balance of dairy cattle in relation to milk production variables and fertility.Crossref | GoogleScholarGoogle Scholar | 10659965PubMed |

Eggen A (2012) The development and application of genomic selection as a new breeding paradigm. Animal Frontiers 2, 10–15.
The development and application of genomic selection as a new breeding paradigm.Crossref | GoogleScholarGoogle Scholar |

Fang Q, Forrest RH, Zhou H, Frampton CM, Hickford JG (2013) Variation in exon 10 of the ovine calpain 3 gene (CAPN3) and its association with meat yield in New Zealand Romney sheep. Meat Science 94, 388–390.
Variation in exon 10 of the ovine calpain 3 gene (CAPN3) and its association with meat yield in New Zealand Romney sheep.Crossref | GoogleScholarGoogle Scholar | 23567141PubMed |

Feldman BJ, Streeper RS, Farese RV, Yamamoto KR (2006) Myostatin modulates adipogenesis to generate adipocytes with favorable metabolic effects. Proceedings of the National Academy of Sciences, USA 103, 15675–15680.
Myostatin modulates adipogenesis to generate adipocytes with favorable metabolic effects.Crossref | GoogleScholarGoogle Scholar |

Glading A, Lauffenburger DA, Wells A (2002) Cutting to the chase: calpain proteases in cell motility. Trends in Cell Biology 12, 46–54.
Cutting to the chase: calpain proteases in cell motility.Crossref | GoogleScholarGoogle Scholar | 11854009PubMed |

Gong H, Zhou H, Hickford JG (2011) Diversity of the glycine/tyrosine-rich keratin-associated protein 6 gene (KAP6) family in sheep. Molecular Biology Reports 38, 31–35.
Diversity of the glycine/tyrosine-rich keratin-associated protein 6 gene (KAP6) family in sheep.Crossref | GoogleScholarGoogle Scholar | 20238170PubMed |

Gu H, Cao Y, Qiu B, Zhou Z, Deng R, Chen Z, Li R, Li X, Wei Q, Xia X, Yong W (2016) Establishment and phenotypic analysis of an Mstn knockout rat. Biochemical and Biophysical Research Communications 477, 115–122.
Establishment and phenotypic analysis of an Mstn knockout rat.Crossref | GoogleScholarGoogle Scholar | 27289021PubMed |

Guo T, Jou W, Chanturiya T, Portas J, Gavrilova O, McPherron AC (2009) Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity. PLoS One 4, e4937
Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity.Crossref | GoogleScholarGoogle Scholar | 19295913PubMed |

Hadjigorgiou I (2014) Sheep and goat farming and rural development in Greece. In ‘Proceeding of CANEPAL conference: celebrating pastoral life’. (Ed. F. Papageorgiou) pp. 72–84. (Heritage and Economic Development: Athens, Greece)

Hauerslev S, Sveen ML, Duno M, Angelini C, Vissing J, Krag TO (2012) Calpain 3 is important for muscle regeneration: evidence from patients with limb girdle muscular dystrophies. BMC Musculoskeletal Disorders 13, 43
Calpain 3 is important for muscle regeneration: evidence from patients with limb girdle muscular dystrophies.Crossref | GoogleScholarGoogle Scholar | 22443334PubMed |

Hickford JG, Forrest RH, Zhou H, Fang Q, Han J, Frampton CM, Horrell AL (2010) Polymorphisms in the ovine myostatin gene (MSTN) and their association with growth and carcass traits in New Zealand Romney sheep. Animal Genetics 41, 64–72.
Polymorphisms in the ovine myostatin gene (MSTN) and their association with growth and carcass traits in New Zealand Romney sheep.Crossref | GoogleScholarGoogle Scholar | 19799595PubMed |

Hilson JA, Rasmussen KM, Kjolhede CL (2004) High pre-pregnant body mass index is associated with poor lactation outcomes among white, rural women independent of psychosocial and demographic correlates. Journal of Human Lactation 20, 18–29.
High pre-pregnant body mass index is associated with poor lactation outcomes among white, rural women independent of psychosocial and demographic correlates.Crossref | GoogleScholarGoogle Scholar | 14974697PubMed |

Hirai S, Matsumoto H, Hino N, Kawachi H, Matsui T, Yano H (2007) Myostatin inhibits differentiation of bovine preadipocyte. Domestic Animal Endocrinology 32, 1–14.
Myostatin inhibits differentiation of bovine preadipocyte.Crossref | GoogleScholarGoogle Scholar | 16431073PubMed |

Honda M, Masui F, Kanzawa N, Tsuchiya T, Toyooka T (2008) Specific knockdown of m-calpain blocks myogenesis with cDNA deduced from the corresponding RNAi. American Journal of Physiology. Cell Physiology 294, C957–C965.
Specific knockdown of m-calpain blocks myogenesis with cDNA deduced from the corresponding RNAi.Crossref | GoogleScholarGoogle Scholar | 18216163PubMed |

Kärst S, Strucken EM, Schmitt AO, Weyrich A, de Villena FP, Yang H, Brockmann GA (2013) Effect of the myostatin locus on muscle mass and intramuscular fat content in a cross between mouse lines selected for hypermuscularity. BMC Genomics 14, 16
Effect of the myostatin locus on muscle mass and intramuscular fat content in a cross between mouse lines selected for hypermuscularity.Crossref | GoogleScholarGoogle Scholar | 23324137PubMed |

Kominakis A, Volanis M, Rogdakis E (2001) Genetic modelling of test day records in dairy sheep using orthogonal Legendre polynomials. Small Ruminant Research 39, 209–217.
Genetic modelling of test day records in dairy sheep using orthogonal Legendre polynomials.Crossref | GoogleScholarGoogle Scholar |

Lin J, Arnold HB, Della-Fera MA, Azain MG, Hartzell DL, Baile CA (2002) Myostatin knock-out in mice increases myogenesis and decreases adipogenesis. Biochemical and Biophysical Research Communications 291, 701–706.
Myostatin knock-out in mice increases myogenesis and decreases adipogenesis.Crossref | GoogleScholarGoogle Scholar |

Liu S, Lau L, Wei J, Zhu D, Zou S, Sun HS, Fu Y, Liu F, Lu Y (2004) Expression of Ca(2+)-permeable AMPA receptor channels primes cell death in transient forebrain ischemia. Neuron 43, 43–55.
Expression of Ca(2+)-permeable AMPA receptor channels primes cell death in transient forebrain ischemia.Crossref | GoogleScholarGoogle Scholar | 15233916PubMed |

Lobley GE (2003) Protein turnover: what does it mean for animal production? Canadian Journal of Animal Science 83, 327–340.
Protein turnover: what does it mean for animal production?Crossref | GoogleScholarGoogle Scholar |

Mazila M (2013) Analysis of effects of negative energy balance in dairy animals using data from three regions of New Zealand’s North Island. MVetSc Thesis, Massey University, Palmerston North, New Zealand.

Mazza S, Guzzo N, Sartori C, Mantovani R (2016) Genetic correlations between type and test-day milk yield in small dual-purpose cattle populations: The Aosta Red Pied breed as a case study. Journal of Dairy Science 99, 8127–8136.
Genetic correlations between type and test-day milk yield in small dual-purpose cattle populations: The Aosta Red Pied breed as a case study.Crossref | GoogleScholarGoogle Scholar | 27448852PubMed |

McPherron AC, Lee SJ (2002) Suppression of body fat accumulation in myostatin-deficient mice. The Journal of Clinical Investigation 109, 595–601.
Suppression of body fat accumulation in myostatin-deficient mice.Crossref | GoogleScholarGoogle Scholar | 11877467PubMed |

McPherron AC, Lawler AM, Lee SJ (1997) Regulation of skeletal muscle mass in mice by a new TGF-b superfamily member. Nature 387, 83–90.
Regulation of skeletal muscle mass in mice by a new TGF-b superfamily member.Crossref | GoogleScholarGoogle Scholar | 9139826PubMed |

McPherron AC, Guo T, Wang Q, Portas J (2012) Soluble activin receptor type IIB treatment does not cause fat loss in mice with diet-induced obesity. Diabetes, Obesity & Metabolism 14, 279–282.
Soluble activin receptor type IIB treatment does not cause fat loss in mice with diet-induced obesity.Crossref | GoogleScholarGoogle Scholar |

Mendias CL, Bakhurin KI, Faulkner JA (2008) Tendons of myostatin-deficient mice are small, brittle, and hypocellular. Proceedings of the National Academy of Sciences, USA 105, 388–393.
Tendons of myostatin-deficient mice are small, brittle, and hypocellular.Crossref | GoogleScholarGoogle Scholar |

Pantoja C, Huff JT, Yamamoto KR (2008) Glucocorticoid signaling defines a novel commitment state during adipogenesis in vitro. Molecular Biology of the Cell 19, 4032–4041.
Glucocorticoid signaling defines a novel commitment state during adipogenesis in vitro.Crossref | GoogleScholarGoogle Scholar | 18653467PubMed |

Raes K, de Smet S, Demeyer D (2001) Effect of double-muscling in Belgian Blue young bulls on the intramuscular fatty acid composition with emphasis on conjugated linoleic acid and polyunsaturated fatty acids. Animal Science 73, 253–260.
Effect of double-muscling in Belgian Blue young bulls on the intramuscular fatty acid composition with emphasis on conjugated linoleic acid and polyunsaturated fatty acids.Crossref | GoogleScholarGoogle Scholar |

Richard I, Broux O, Allamand V, Fougerousse F, Chiannilkulchai N, Bourg N, Brenguier L, Devaud C, Pasturaud P, Roudaut C (1995) Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A. Cell 81, 27–40.
Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.Crossref | GoogleScholarGoogle Scholar |

Rothschild MF, Ruvinsky A (2007) Marker-assisted selection for aquaculture species. Chapter 12. In ‘Aquaculture genome technologies’. (Ed. Z Liu) pp. 201–216. (Blackwell Publishing: Oxford, UK)

Rutishauser IH, Carlin JB (1992) Body mass index and duration of breast feeding: a survival analysis during the first six months of life. Journal of Epidemiology and Community Health 46, 559–565.
Body mass index and duration of breast feeding: a survival analysis during the first six months of life.Crossref | GoogleScholarGoogle Scholar | 1494068PubMed |

Samuel RS, Moehn S, Pencharz PB, Ball RO (2009) Protein turnover in lactating sows. Advances in Pork Production 20, Abstract #5

Sartori C, Guzzo N, Mazza S, Mantovani R (2018) Genetic correlations among milk yield, morphology, performance test traits and somatic cells in dual-purpose Rendena breed. Animal 12, 906–914.
Genetic correlations among milk yield, morphology, performance test traits and somatic cells in dual-purpose Rendena breed.Crossref | GoogleScholarGoogle Scholar | 29039278PubMed |

SAS (2004) SAS user’s guide, version 9.1. (Statistical Analysis System Institute: Cary, NC, USA)

Szabo G, Dallmann G, Muller G, Patthy L, Soller M, Varga L (1998) A deletion in the myostatin gene causes the compact (Cmpt) hypermuscular mutation in mice. Mammalian Genome 9, 671–672.
A deletion in the myostatin gene causes the compact (Cmpt) hypermuscular mutation in mice.Crossref | GoogleScholarGoogle Scholar | 9680391PubMed |

Tang L, Yang X, Gao X, Du H, Han Y, Zhang D, Wang Z, Sun L (2016) Inhibiting myostatin signaling prevents femoral trabecular bone loss and microarchitecture deterioration in diet-induced obese rats. Experimental Biology and Medicine (Maywood, N.J.) 241, 308–316.
Inhibiting myostatin signaling prevents femoral trabecular bone loss and microarchitecture deterioration in diet-induced obese rats.Crossref | GoogleScholarGoogle Scholar |

Tzanidakis N, Voutzourakis N, Stefanakis A, Brozas C, Sotiraki S, Kiossis E (2017) Effect of management factors on reproductive and milk production performance of a dairy sheep breed adapted to low-input management systems. Journal of the Hellenic Veterinary Medical Society 68, 67–78.
Effect of management factors on reproductive and milk production performance of a dairy sheep breed adapted to low-input management systems.Crossref | GoogleScholarGoogle Scholar |

Villanueva B, Pong-Wong R, Fernández J, Toro MA (2005) Benefits from marker assisted selection under an additive polygenic genetic model. Journal of Animal Science 83, 1747–1752.
Benefits from marker assisted selection under an additive polygenic genetic model.Crossref | GoogleScholarGoogle Scholar | 16024693PubMed |

Whittemore LA, Song K, Li X, Aghajanian J, Davies M, Girgenrath S, Hill JJ, Jalenak M, Kelley P, Knight A, Maylor R, O’Hara D, Pearson A, Quazi A, Ryerson S, Tan X, Tomkinson KN, Veldman GM, Widom A, Wright JF, Wudyka S, Zhao L, Wolfman NM (2003) Inhibition of myostatin in adult mice increases skeletal muscle mass and strength. Biochemical and Biophysical Research Communications 300, 965–971.
Inhibition of myostatin in adult mice increases skeletal muscle mass and strength.Crossref | GoogleScholarGoogle Scholar | 12559968PubMed |

Zhang Z, Larner SF, Liu MC, Zheng W, Hayes RL, Wang KK (2009) Multiple alphaII-spectrin breakdown products distinguish calpain and caspase dominated necrotic and apoptotic cell death pathways. Apoptosis 14, 1289–1298.
Multiple alphaII-spectrin breakdown products distinguish calpain and caspase dominated necrotic and apoptotic cell death pathways.Crossref | GoogleScholarGoogle Scholar | 19771521PubMed |

Zhao B, Wall RJ, Yang J (2005) Transgenic expression of myostatin propeptide prevents diet-induced obesity and insulin resistance. Biochemical and Biophysical Research Communications 337, 248–255.
Transgenic expression of myostatin propeptide prevents diet-induced obesity and insulin resistance.Crossref | GoogleScholarGoogle Scholar | 16182246PubMed |

Zhou H, Hickford JG, Fang Q (2006) A two-step procedure for extracting genomic DNA from dried blood spots on filter paper for polymerase chain reaction amplification. Analytical Biochemistry 354, 159–161.
A two-step procedure for extracting genomic DNA from dried blood spots on filter paper for polymerase chain reaction amplification.Crossref | GoogleScholarGoogle Scholar | 16643836PubMed |

Zhou H, Frampton CM, Hickford JG (2009) Variation in ovine CAPN3 is not associated with meat tenderness. Animal Genetics 40, 251–252.
Variation in ovine CAPN3 is not associated with meat tenderness.Crossref | GoogleScholarGoogle Scholar | 19133936PubMed |