Overview

Also Known As:129.MOLF-Chr19 consomic (or M19), CSSM19, CSS-M19, M19

Homosomic males from the chromosome 19 consomic strain 129S1/SvImJ-Chr19^MOLF/Ei/NadJahe (also called 129.MOLF-Chr19 or M19) exhibit ~75% spontaneous testicular germ cell tumors (TGCTs). These mice are useful for studying susceptibility to TGCT - the most common solid tumors in human males aged 15–34.
This strain represents one of a panel of inter-species chromosome substitution (or consomic) strains. Each strain carries a chromosome from the Mus musculus molossinus wild-derived strain MOLF/Ei introgressed into a Mus musculus domesticus 129S1/SvImJ background. These strains provide a tool for dissection of quantitative trait loci.

Donating Investigator

Jason D Heaney, Baylor College of Medicine

Genetic overview

Genetic Background	Generation

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Research Applications

Cancer Research
Reproductive Biology Research
Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The chromosome 19 consomic strain 129S1/SvImJ-Chr19^MOLF/Ei/NadJahe (also called 129.MOLF-Chr19 or M19) represents one of a panel of inter-species chromosome substitution (or consomic) strains. Each strain carries a chromosome from the Mus musculus molossinus wild-derived strain MOLF/Ei introgressed into a Mus musculus domesticus 129S1/SvImJ background. The MOLF strain is separated from the common inbred strain progenitors by approximately 100,000 years. These strains represent a tool for dissection of quantitative trait loci.

The M19 mice are useful for studying genetic susceptibility to testicular germ cell tumors (TGCTs) - the most common solid tumors in human males aged 15–34. Homosomic and heterozygous M19 males have a spontaneous TGCT rate of ~75% and ~25%, respectively, whereas the incidence ~5% in 129S1/SvImJ males. Spontaneous TGCTs have not been observed in MOLF/Ei. For homosomic M19 males, unilateral and bilateral primary tumors are observed, and putative metastases have been reported. M19 males are fertile, but may exhibit some breeding difficulties if large tumors are present (details below). For homosomic M19 females, there is no evidence for reduced fertility (no germ cell defects have been detected).

Whereas 129 mice homozygous for the Dnd1^Ter mutation (129T1/Sv-Oca2⁺ Tyr^c-ch Dnd1^Ter/J ; Stock No. 000091) have a TGCT incidence of ~90% and are also deficient for normal germ cells, these homosomic M19 males show most germ cells develop normally. Thus, both normal and transformed germ cells are present in the M19 testis, and M19 males can be fertile despite having testicular tumors.

In M19 males, the window of TGCT initiation is during embryogenesis (embryonic day (E)12.5-15.5). ~75% of M19 males develop tumors in utero and that incidence does not increase with age. At E15.5, the tumor stem cells (pluripotent embryonal carcinoma [EC] cells) first appear and form foci of cells. By E18.5, the EC cells have started to differentiate into cell types derived from all three embryonic germ layers (teratoma). Histologically, various stages of tumor progression are visible from ~E15.5 onward. The donating investigator reports that gross visual observation of testicular tumors is reliable by 6-8 weeks of age. Tumors grow for a while after birth, but because they ultimately form mature teratomas (i.e., contain fully differentiated cell types), the cells eventually become quiescent and the tumor stops growing (or may even regress). Tumor size is random: some adult males exhibit very large tumors - but this has no correlation with advancing age.

Multiple TGCT susceptible loci have been mapped to chromosome 19 of the M19 strain. These loci either act independently or interact epistatically to contribute to testicular tumor development. Susceptibility genes/variants exist in both the donor (MOLF/Ei) and host (129S1/SvImJ) genome. Several publications examine M19 testicular germ cell tumor quantitative trait loci and/or specific genes (Youngren et al. 2003 Hum Mol Genet 12:389,
Zhu et al. 2007 Mamm Genome 18:584 and
Zhu et al. 2010 Cancer Res 70:7264).

Development

The laboratory of Dr. Joseph Nadeau (Case Western Reserve University) developed the 129S1/SvImJ-Chr #^MOLF/Ei/Nad strain set by replacing individual chromosomes from the MOLF/Ei donor strain into the 129S1/SvImJ host strain using a marker-assisted series of backcrosses.

Using this approach, the chromosome 19 consomic strain 129S1/SvImJ-Chr19^MOLF/Ei/NadJahe (also called 129.MOLF-Chr19 or M19) was created by Dr. Angabin Matin while in the laboratory of Dr. Nadeau. At backcross generations three and four, females with non-recombinant MOLF/Ei-derived chromosome 19 were crossed with 129S1/SvImJ males - thus the Y chromosome of the consomic strain is of 129S1/SvImJ origin. After working with the M19 mice in Dr. Nadeau's lab, Dr. Jason D. Heaney transferred the mice to Baylor College of Medicine in 2012. From there, homosomic mice (both females and males) with agouti coat color were sent to The Jackson Laboratory in 2017.

Control Suggestions

Approximate Controls

002448 129S1/SvImJ

Additional Information

Considerations for Choosing Controls

Selected References

Anderson PD; Nelson VR; Tesar PJ; Nadeau JH. 2009. Genetic factors on mouse chromosome 18 affecting susceptibility to testicular germ cell tumors and permissiveness to embryonic stem cell derivation. Cancer Res 69(23):9112-7PubMed: 19934337 MGI: J:155049

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Genetics

Currently there are no related genes or alleles for this strain.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Cancer Research
- Increased Tumor Incidence
  - Gonadal Tumors: testicular teratomas
  - Gonadal Tumors
- Tumor Resistance
- Tumor Suppressor Genes
- Oncogenes
Reproductive Biology Research
- Gonadal Tumors
  - testicular teratomas
Research Tools
- Cancer Research
  - anti-tumor activity
  - tumor immunology

Mammalian Phenotype Terms by Genotype

References

Anderson PD; Nelson VR; Tesar PJ; Nadeau JH. 2009. Genetic factors on mouse chromosome 18 affecting susceptibility to testicular germ cell tumors and permissiveness to embryonic stem cell derivation. Cancer Res 69(23):9112-7PubMed: 19934337 MGI: J:155049

Additional References

Heaney JD; Anderson EL; Michelson MV; Zechel JL; Conrad PA; Page DC; Nadeau JH. 2012. Germ cell pluripotency, premature differentiation and susceptibility to testicular teratomas in mice. Development 139(9):1577-86PubMed: 22438569 MGI: J:184020
Youngren KK; Nadeau JH; Matin A. 2003. Testicular cancer susceptibility in the 129.MOLF-Chr19 mouse strain: additive effects, gene interactions and epigenetic modifications. Hum Mol Genet 12(4):389-98PubMed: 12566386 MGI: J:81573
Zechel JL; MacLennan GT; Heaney JD; Nadeau JH. 2011. Spontaneous metastasis in mouse models of testicular germ-cell tumours. Int J Androl 34(4 Pt 2):e278-87PubMed: 21651572 MGI: J:235639
Zhu R; Heaney J; Nadeau JH; Ali S; Matin A. 2010. Deficiency of splicing factor 1 suppresses the occurrence of testicular germ cell tumors. Cancer Res 70(18):7264-72PubMed: 20736371 MGI: J:164224

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Breeding Considerations

This chromosome 19 consomic strain 129S1/SvImJ-Chr19^MOLF/Ei/NadJahe (also called 129.MOLF-Chr19 or M19) is maintained as homozygous (homosomic) for the MOLF/Ei-derived chromosome 19 by sibling matings.
Homosomic and heterozygous M19 males have a spontaneous testicular germ cell tumor (TGCT) rate of ~75% and ~25%, respectively, and are fertile despite having testicular tumors. However, homosomic males may exhibit some breeding difficulties if large tumors are present. For homosomic M19 females, there is no evidence for reduced fertility (no germ cell defects have been detected). In general, mouse lines on the 129 genetic background typically have smaller litters sizes.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the 129.MOLF-Chr19 consomic (or M19) mouse strain in a publication, please cite the originating article(s) and include JAX stock #029319 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous for Chr 19<MOLF/Ei> 1pr minimum

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