Increased prenatal IGF2 expression due to the porcine IGF2 intron3-G3072A mutation may be responsible for increased muscle mass1

Abstract

A SNP (IGF2 G3072A) within intron 3 of disrupts a binding site for the repressor zinc finger BED-type containing 6 (ZBED6), leading to increased carcass lean yields in pigs. However, the relative contributions of prenatal as opposed to postnatal increased IGF2 expression are unclear. As muscle fiber number is set at birth, prenatal and neonate skeletal muscle development is critical in determining mature growth potential. Therefore, the objectives of this study were to determine the contributions of hyperplasia and hypertrophy to increased muscle mass and to delineate the effect of the mutation on the expression of myogenic genes during prenatal and postnatal growth. Sows (IGF2 A/A) were bred to a single heterozygous (IGF2 A/G) boar. For fetal samples, sows were euthanized at 60 and 90 d of gestation (d60 and d90) to obtain fetuses. Male and female offspring were also euthanized at birth (0d), weaning (21d), and market weight of approximately 130 kg (176d). At each sampling time, the LM, psoas major (PM), and semitendinosus (ST) muscles were weighed. Samples of the LM were used to quantify the expression of IGF family members, myogenic regulatory factors (MRF), myosin heavy chain isoforms, and growth factors, myostatin, and . Liver samples were used to quantify and expression. At 176d, weights of LM, PM, and ST muscles were all increased approximately 8% to 14% (P < 0.01) in pigs with paternal A (A(Pat)) alleles compared with those with paternal G (G(Pat)) alleles. Additionally, total muscle fiber number in the ST at 176d tended to be greater (P = 0.10), whereas muscle fiber cross-sectional area tended to be reduced ( P= 0.08) in A(Pat) pigs compared with G(Pat) pigs. In addition to the expected 2.7- to 4.5-fold increase (P ≤ 0.02) in expression in the LM in A(Pat) compared with G(Pat) pigs at postnatal sampling times (21d and 176d), IGF2 expression was also increased (P ≤ 0.06) 1.4- to 1.5-fold at d90 of gestation and at birth. At d90, expression of myogenic factor 5 (MYF5), a MRF expressed in proliferating myoblasts, in the LM was greater (P = 0.01) in A (Pat) pigs than in G(Pat) pigs. Interestingly, at 21d hepatic expression was greater (P = 0.01), whereas expression decreased (P = 0.01) in A(Pat) pigs compared with G(Pat) pigs; however, there were no differences (P ≥ 0.18) in hepatic expression between genotypes at 0d and 176d. These data suggest that prenatal hyperplasia of muscle fibers stimulated by increased IGF2 expression may contribute to increased muscle mass of A(Pat) pigs.

Elevated insulin-like growth factor 2 expression may contribute to the hypermuscular phenotype of myostatin null mice

“…A SNP within intron 3 of the paternal Igf2 allele in pigs has been associated with increased leanness and decreased fat accumulation [10]. Pigs with the 'A' allele have greater postnatal Igf2 expression compared with those with the wild type 'G' allele [20]. Given the increase in muscle hypertrophy in IGF2 'A' pigs, we hypothesized that increased postnatal muscle hypertrophy in MN mice may also be associated with elevated Igf2 levels.…”

Molecular and functional heterogeneity of early postnatal porcine satellite cell populations is associated with bioenergetic profile

“…Primers for the amplification of the myogenic marker genes sus scrofa (sc) Pax7 27, scMyf5 27, scMyoD 27, scMyoG 58, scDesmin 59, and sc embryonic Myosin (eMyH )60 were used. Appropriate primer-annealing conditions for real-time quantitative PCR (qRT-PCR) were assessed for each respective primer pair by a temperature gradient PCR (tg-PCR) in a MasterCycler nexus gradient (Eppendorf) and an agarose electroseparation of respective amplicons.…”

Transcriptome Analysis Reveals the Long Intergenic Noncoding RNAs Contributed to Skeletal Muscle Differences between Yorkshire and Tibetan Pig

“…More importantly, we found that DEL-MSTRG.8035 is positively related to the expression of MCU and highly expressed in the LW group. Insulin-like growth factor 2 (IGF-2) is a maternal blotting growth factor that regulates prenatal skeletal muscle development [27]. It can be involved in the IGF1-Akt-mTOR signaling pathway by activating the IGF1 receptor [28].…”