Tissue-specific, inducible and functional expression of the E alpha d MHC class II gene in transgenic mice.

Pinkert, Carl A.; Widera, Georg; Cowing, Carol; Heber‐Katz, Ellen; Palmiter, Richard D.; Flavell, Richard A.; Brinster, Ralph L.

doi:10.1002/j.1460-2075.1985.tb03918.x

Cited by 69 publications

(21 citation statements)

References 41 publications

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“…The recessive nature of this mutation is in contrast to other previously identified examples of male sterility in transgenic mice, where the defect was inherited in a dominant fashion (31)(32)(33)(34).…”

contrasting

confidence: 70%

Symplastic spermatids (sys): a recessive insertional mutation in mice causing a defect in spermatogenesis.

MacGregor

Russell

Beek

et al. 1990

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

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A line of transgenic mice that carries an insertional mutation in a gene essential for spermatogenesis is described. Males homozygous for the transgenic insert are sterile, while female homozygotes and both male and female heterozygotes exhibit normal fertility. Developing spermatids in homozygous males form prominent abnormal multinucleated syncytia (symplasts) and do not complete maturation. In addition, abnormal cytoplasmic vacuolation is commonly seen in Sertoli cells. One flank of the transgenic integration site within the genome has been cloned and used to show linkage between homozygosity for the transgene and the mutant phe-

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contrasting

confidence: 70%

Symplastic spermatids (sys): a recessive insertional mutation in mice causing a defect in spermatogenesis.

MacGregor

Russell

Beek

et al. 1990

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

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“…on May 10, 2018 by guest http://mcb.asm.org/ Downloaded from first attributed to the expression of E. d (37). However the cosmid also carried an HSV-1 tk gene, and sterility was later found to be due to the expression of this gratuitous component of the construct (7).…”

mentioning

confidence: 99%

The herpes simplex virus type 1 thymidine kinase is expressed in the testes of transgenic mice under the control of a cryptic promoter.

Al‐Shawi¹,

Burke²,

Wallace³

et al. 1991

Mol. Cell. Biol.

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We reported previously that the herpes simplex virus type 1 (HSV-1) thymidine kinase reporter gene (tk) was expressed in the testes of transgenic mice when coupled to the promoter of a liver-specific mouse major urinary protein (MUP) gene. Here we show that HSV-1 tk is also expressed in the testis when coupled to a MUP pseudogene promoter, to a truncated MUP promoter that is not active in the liver, and to the promoter of the bovine thyroglobulin gene. Furthermore, HSV-1 tk itself was expressed in the testis, although its normal expression had been disabled by removing an upstream regulator of transcription. In every case, the same multiple transcripts were observed, with their 5' ends located downstream of the normal HSV-1 tk translation initiation codon. We conclude that the transcription of HSV-1 tk in the testis is directed by a cryptic TATA box-independent promoter located in the coding region of the gene. The longest HSV-1 thymidine kinase (TK) polypeptides synthesized in the testis were shorter than full-length TK and probably result from translational initiation at Met46 and Met6o, the second and third ATG codons of the tk reading frame. Male mice of most transgenic lines were sterile, and the severity of the lesion in spermatogenesis was directly related to the level of TK expression. In the most highly expressing lines, sperm counts were low and morphologically defective sperm were common. In other sterile lines, TK was expressed at a lower level and sperm counts were normal but sperm motility was greatly reduced. Lines with the lowest levels of HSV-1 TK expression were fertile. HSV-1 TK was expressed in germ line cells, mainly in the haploid spermatids. However, low-level HSV-1 TK activity was found in the testis before the first germ cells entered meiosis, showing that if expression is confined to the germ cells, it also occurs in spermatogonia.

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“…It has recently been demonstrated that insertion of a number of tissue-specific genes into the mouse genome resulted in both tissue-and stagespecific expression of genes in transgenic mice, indicating that these genes responded to the developmental signals of the host (4,6,9,11,13,15,17,18,23,24,27,28,30,(33)(34)(35)39).…”

mentioning

confidence: 99%

Tissue-specific and developmentally regulated expression of a chimeric actin-globin gene in transgenic mice.

Shani¹

1986

Mol. Cell. Biol.

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A chimeric plasmid containing about 2/3 of the rat skeletal muscle actin gene plus 730 base pairs of its 5' flanking sequences fused to the 3' end of a human embryonic globin gene (D. Melloul, B. Aloni, J. Calvo, D. Yaffe, and U. Nudel, EMBO J. 3:983-990, 1984) was inserted into mice by microinjection into fertilized eggs. Eleven transgenic mice carrying the chimeric gene with or without plasmid pBR322 DNA sequences were identified. The majority of these mice transmitted the injected DNA to about 50% of their progeny. However, in transgenic mouse CV1, transmission to progeny was associated with amplification or deletion of the injected DNA sequences, while in transgenic mouse CV4 transmission was distorted, probably as a result of insertional mutagenesis. Tissue-specific expression was dependent on the removal of the vector DNA sequences from the chimeric gene sequences prior to microinjection. None of the transgenic mice carrying the chimeric gene together with plasmid pBR322 sequences expressed the introduced gene in striated muscles. In contrast, the six transgenic mice carrying the chimeric gene sequences alone expressed the inserted gene specifically in skeletal and cardiac muscles. Moreover, expression of the chimeric gene was not only tissue specific, but also developmentally regulated. Similar to the endogenous skeletal muscle actin gene, the chimeric gene was expressed at a relatively high level in cardiac muscle of neonatal mice and at a significantly lower level in adult cardiac muscle. These results indicate that the injected DNA included sufficient cis-acting control elements for its tissue-specific and developmentally regulated expression in transgenic mice.

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Tissue-specific, inducible and functional expression of the E alpha d MHC class II gene in transgenic mice.

Cited by 69 publications

References 41 publications

Symplastic spermatids (sys): a recessive insertional mutation in mice causing a defect in spermatogenesis.

Symplastic spermatids (sys): a recessive insertional mutation in mice causing a defect in spermatogenesis.

The herpes simplex virus type 1 thymidine kinase is expressed in the testes of transgenic mice under the control of a cryptic promoter.

Tissue-specific and developmentally regulated expression of a chimeric actin-globin gene in transgenic mice.

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