Recent studies on nucleotide sequences encoding the caseins

Bonsing, J; Mackinlay, Antony G.

doi:10.1017/s0022029900025632

Cited by 59 publications

(29 citation statements)

References 39 publications

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“…Analysis of the patterns of inheritance of these allelic variants, together with those of the other caseins, indicates that the genes for all four caseins occur as a tightly linked cluster [6,71. Analysis of the bovine casein genes as the cDNA level, as well as of their homologues in other species, reviewed in [8], has confirmed that the genes for the three calcium-sensitive caseins are evolutionarily related and constitute a small gene family. It appears that the ti-casein gene, although linked to the other casein genes, is unrelated to them.…”

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confidence: 92%

Isolation and characterization of the bovine k‐casein gene

Alexander

Stewart

Mackinlay

et al. 1988

European Journal of Biochemistry

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154

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1. The bovine ti-casein gene has been isolated as a series of overlapping I clones and shown to consist of five exons distributed over a total length of approximately 13 kb. Most of the mature protein-coding sequence is contained in a single large exon.2. Approximately 65% of the gene has been sequenced together with portions of the 5'-and 3'-flanking sequences. The immediate 5'-flanking sequence contains several motifs which are characteristic of upstream regions including a TATA box, a CAAT box, a sequence similar to that recognized by transcription factor AP-1 and a purine-rich sequence resembling that found upstream in all other lactoprotein genes. Other possible regulatory sequences are found upstream of exon 4.3. The organization of the K-casein gene, together with its upstream sequence, confirms previous conclusions that it is unrelated to the calcium-sensitive-casein gene familiy to which it is linked. Evidence is presented which supports a previous suggestion that ic-casein and the fibrinogens are evolutionarily related.4. Intron sequences contain several examples of the A family of the artiodactyl Alu-like repeated sequences, together with a single example of a C-family sequence. The remainders of the introns of the rc-casein gene, compared with the repeat elements and exons, are A + T-rich.5. Among the I clones isolated, representatives were found of the A and B genetic variants which can be distinguished by restriction-enzyme analysis. Several other examples of polymorphisms in the non-coding region were found.The caseins are the predominant proteins in the milk of most species. As well as being the main source of amino acids for the suckling infant, the caseins serve to raise the calcium and phosphate concentrations in milk to levels well in excess of the solubility product of calcium phosphate by forming loosely ordered aggregates, termed micelles, which sequester calcium phosphate. Bone formation in the young animal thus depends on the ability of casein to transport appropriate quantities of calcium phosphate in milk.In bovine milk more than 20 individual components can be resolved when whole casein is analyzed electrophoretically under dissociating conditions [I]. These result from posttranslational modification and genetic variation of four primary translation products which correspond to asl-, clS2-, pand k--caseins. The xsl-, xs2-and p-caseins are insoluble in the presence of calcium ion at the concentrations at which it occurs in milk and these caseins are referred to as the calciumsensitive caseins. In contrast, K-casein is insensitive to the presence of calcium and is referred to as the micelle stabilizer because it is essential for the formation of stable casein micelles [2]. Following ingestion, the caseins are immobilized in the stomach as a result of clot formation. This occurs when chymosin (rennin) or pepsin specifically cleaves a single PheMet bond in K-casein to form insoluble para-K-casein (105 residues) and a soluble macropeptide containing the C-termind 64 amino acid residues of ...

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confidence: 92%

Isolation and characterization of the bovine k‐casein gene

Alexander

Stewart

Mackinlay

et al. 1988

European Journal of Biochemistry

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154

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“…Caseins appear to be a rapidly evolving gene family, presumably due to the minimal structural requirements for function (Bonsing and Mackinlay, 1987). However, in contrast to the calcium-sensitive α s1 -, β-, and α s2 -caseins, the κ-casein fraction plays a crucial role in the formation, stabilization, and aggregation of the casein micelles and thus affects the technological (Mariani et al, 1976;Aleandri et al, 1990;Lodes et al, 1996;Falaki et al, 1997) and nutritional properties of milk (Mercier et al, 1973(Mercier et al, , 1976Malkoski et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Caprine κ-Casein (CSN3) Polymorphism: New Developments in Molecular Knowledge

Prinzenberg

Gutscher

Chessa

et al. 2005

Journal of Dairy Science

107

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A high degree of polymorphism was recently found at the κ-casein (CSN3) locus in the domesticated goat (Capra hircus). In the present study, 2 new patterns previously identified by PCR-single-strand conformation polymorphism analysis (SSCP) were characterized. The allele provisionally named "X" (GenBank Accession no. AY350425) differs from CSN3*C (AF485341) by a (silent) A→G substitution at position 509 of the goat CSN3 reference sequence (X60763). As this newly identified sequence changes the amino acid sequence, and the already known CSN3*C allele (AF485341) has an additional silent mutation, we proposed a change in nomenclature to reflect these changes, indicating the silent mutation with the prime symbol (i.e., ′). The CSN3*M allele (provisionally named "Y") results in a new protein variant, differing by 2 nonsynonymous mutations from the CSN3*F allele. The new variant is characterized by a G→A transition at nucleotide position 384, resulting in the amino acid exchange Asp 90 →Asn 90 , and a C→T transition at position 550, resulting in a Val 145 →Ala 145 substitution. Thus, the number of alleles identified in the domesticated goat has increased to 16, of which 13 are protein variants and 3 are silent mutations, involving a total of 15 polymorphic sites in CSN3 exon 4. Data on the distribution of the main alleles in 7 goat breeds of Europe, West Africa, and the Near East show differences in the occurrence and frequency of the alleles between breeds and geographic origin with the highest number of alleles found in goat breeds from the Near East. (Key words: goat, κ-casein polymorphism, singlestrand conformation polymorphism, nomenclature) Abbreviation key: CSN3 = κ-casein gene, dsPCR = double-stranded PCR product, IEF = isoelectric focusing, IP = isoelectric point, SSCP = single-strand confor-

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“…Sequences of the casein genes are poorly conserved during evolution (2,3,28). Of all of the caseins, -casein is the most conserved in terms of its molecular architecture.…”

Section: Discussionmentioning

confidence: 99%

κ-Casein-deficient mice fail to lactate

Shekar

Goel

Rani

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Acquisition of milk production capabilities by an ancestor of mammals is at the root of mammalian evolution. Milk casein micelles are a primary source of amino acids and calcium phosphate to neonates. To understand the role of -casein in lactation, we have created and characterized a null mouse strain (Csnk ؊/؊ ) lacking this gene. The mutant -casein allele did not affect the expression of other milk proteins in Csnk ؊/؊ females. However, these females did not suckle their pups and failed to lactate because of destabilization of the micelles in the lumina of the mammary gland. Thus, -casein is essential for lactation and, consequently, for the successful completion of the process of reproduction in mammals. In view of the extreme structural conservation of the casein locus, as well as the phenotype of Csnk ؊/؊ females, we propose that the organization of a functional -casein gene would have been one of the critical events in the evolution of mammals. Further, -casein variants are known to affect the industrial properties of milk in dairy animals. Given the expenses and the time scale of such experiments in livestock species, it is desirable to model the intended genetic modifications in mice first. The mouse strain that we have created would be a useful model to study the effect of -casein variants on the properties of milk and͞or milk products.casein locus ͉ evolution ͉ lactation ͉ milk ͉ micelle M ilk production is an essential component of the reproductive strategy of mammals. The development of a zygote into an organism is accompanied by the preparation of milk synthesis potential by the mammary gland. Perinatal survival in mammals is solely dependent on the availability of milk from the mother. Caseins account for Ͼ80% of the total milk proteins (1). These proteins exist as micelles, consisting of three to four phosphoproteins (i.e., the calcium-sensitive caseins: ␣-, ␤-, ␥-, and ␦-casein in mice) and a calcium-insensitive phosphoglycoprotein, -casein (2). In addition to functioning as the primary source of amino acids, one of the key functions of micelles is to sequester large amounts of calcium phosphate from the maternal diet or bodily stores and make it readily available to the newborn. Calcium-sensitive casein genes seem to have evolved from a primitive casein gene through gene duplication and exon shuffling (3); however, it appears that -casein is not related structurally and evolutionarily to these genes. Instead, it appears to be related to ␥-fibrinogen (4, 5). Recently, it has also been speculated that both the calcium-sensitive and the calciuminsensitive casein gene belong to one gene family (6). The null mutation of the ␤-casein gene in mice (7) and that of ␣ S1 -casein in goats (8) do not show any significant effect on milk micelle formation and lactation. The lack of adverse effects on micelle formation in these mutants suggests functional redundancy amongst calcium-sensitive caseins. However, the absence of ␣ S1 -casein in goats does affect the rate of transport of caseins. The experimental ev...

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Recent studies on nucleotide sequences encoding the caseins

Abstract: Introduction Methodology Casein cDNA sequences The

Cited by 59 publications

References 39 publications

Isolation and characterization of the bovine k‐casein gene

Isolation and characterization of the bovine k‐casein gene

Caprine κ-Casein (CSN3) Polymorphism: New Developments in Molecular Knowledge

κ-Casein-deficient mice fail to lactate

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