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| 2. |
- Liljander, Maria, et al.
(författare)
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Identification of collagen-induced arthritis loci in aged multiparous female mice.
- 2006
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 8:2, s. 45-45
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Tidskriftsartikel (refereegranskat)abstract
- Collagen-induced arthritis in mice is one of the most commonly used autoimmune experimental models, with many similarities to rheumatoid arthritis. Since collagen-induced arthritis is a complex polygenic disease there is a need for identification of several major disease-controlling genes. Because rheumatoid arthritis particularly affects aged women, we have in the present study identified new genetic regions critical for collagen-induced arthritis by studying aged female mice of a cross between NFR/N and B10.Q (H-2q haplotype). The mice in the present study had different reproductive histories, which did not significantly affect the onset, incidence or severity of the disease. A total of 200 female mice were used in a total genome-wide screening with 125 microsatellite markers. We found one new significant quantitative trait locus affecting the arthritis incidence, severity and day of onset on chromosome 11 (denoted Cia40), which colocalizes with a locus controlling pregnancy failure. Furthermore, a quantitative trait locus of suggestive significance associated with the incidence, severity and day of onset was identified on chromosome 1. Finally, a suggestively significant quantitative trait locus associated with collagen type II antibody titers was identified on chromosome 13. This study indicates that several gene loci control arthritis in aged multiparous females, and that at least one of these loci coincides with pregnancy failure.
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| 3. |
- Liljander, Maria, et al.
(författare)
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Identification of Genetic Regions of Importance for Reproductive Performance in Female Mice.
- 2006
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 173:2, s. 901-909
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Tidskriftsartikel (refereegranskat)abstract
- Both environmental and genetic factors can dramatically affect reproductive performance in mice. In this study we have focused on the identification of genetic regions, quantitative trait loci (QTL), which affect the breeding capacity of female mice. We have identified polymorphic microsatellite markers for the mouse strains used and performed a genomewide scan on 237 females from a gene-segregating backcross between a high breeder and a relatively poor breeder. The high-breeder mouse strain we used is the inbred NFR/N mouse (MHC haplotype H-2q), which has extraordinary good breeding properties. The moderate breeder chosen for F(1) and N2 progeny was B10.Q, which is a genetically well-characterized MHC-congenic mouse of the H-2q haplotype. Each of the 237 females of the N2 generation was allowed to mate twice with MHC-congenic B10.RIII (H-2r) males and twice with B10.Q males. A predetermined number of phenotypes related to reproductive performance were recorded, and these included litter size, neonatal growth, and pregnancy rate. Loci controlling litter size were detected on chromosomes 1 (Fecq3) and 9 (Fecq4). The neonatal growth phenotype was affected by Fecq3 and a locus on chromosome 9 (Neogq1). On chromosome 11 two loci affecting the pregnancy rate (Pregq1 and Pregq2) were identified. Furthermore, on chromosomes 13 and 17 we found loci (Pregq3 and Pregq4) influencing the outcome of allogeneic pregnancy (allogeneic by means of MHC disparity between mother and fetuses). A locus on chromosome 1 affecting maternal body weight was also identified and has been denoted Bwq7. It is well known that reproductive performance is polygenically controlled, and the identification of the major loci in this complex process opens the possibility of investigating the natural genetic control of reproduction.
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| 4. |
- Liljander, Maria, et al.
(författare)
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Increased litter size and super-ovulation rate in congenic C57BL mice carrying a polymorphic fragment of NFR/N origin at the Fecq4 locus of chromosome 9.
- 2009
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Ingår i: Genetical Research. - 1469-5073. ; 91:4, s. 259-265
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Tidskriftsartikel (refereegranskat)abstract
- By analysing N2 mice from a cross between the inbred C57BL strain B10.Q and the NMRI-related NFR/N strain, we recently identified a quantitative trait locus (QTL) influencing litter size. This locus is now denoted Fecq4, and it is present on the murine chromosome 9. In the present paper, we describe how the Fecq4 fragment originating form the NFR/N mouse strain will affect B10.Q mice by means of breeding capacity, super-ovulation rate and embryonic development in vitro. Our results show that both the breeding capacity (number of pups produced/breeding cage during a 5 months period) and the mean litter size are significantly increased in B10.Q.NFR/N-Fecq4 congenic mice. Furthermore. B10.Q.NFR/N-Fecq4 congenic mice (both homozygous and heterozygous) did respond much better to super-ovulation than wild-type mice, resulting in a dramatically increased yield of fertilized 1-cell embryos. In addition, embryos containing the Fecq4 fragment were easy to cultivate in vitro, resulting in a higher yield of embryos reaching the blastocyst stage. We propose that B10.Q.NFR/N-Fecq4 congenic mice may be used to improve breeding or super-ovulation rate in different types of genetically modified mice (on C57BL background) that exhibit severe breeding problems. The Fecq4 fragment has been described in detail, and the possible role of polymorphic candidate genes near the linkage peak (58 Mb) has been discussed. Genes of the cytochrome P450 family (1, 11 and 19), such as Cyp19a1, are assumed to be particularly interesting, since they are known to exhibit female-associated reproductive phenotypes, affecting the ovulation rate, if mutated.
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| 5. |
- Liljander, Maria, et al.
(författare)
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Increased susceptibility to collagen-induced arthritis in female mice carrying congenic Cia40/Pregq2 fragments.
- 2008
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: INTRODUCTION: Collagen-induced arthritis (CIA) in mice is a commonly used experimental model for rheumatoid arthritis (RA). We have previously identified a significant quantitative trait locus denoted Cia40 on chromosome 11 that affects CIA in older female mice. This locus colocalizes with another locus, denoted Pregq2, known to affect reproductive success. The present study was performed to evaluate the role of the Cia40 locus in congenic B10.Q mice and to identify possible polymorphic candidate genes, which may also be relevant in the context of RA. METHODS: Congenic B10.Q mice carrying an NFR/N fragment surrounding the Cia40/Pregq2 loci were created by 10 generations of backcrossing (N10). The congenic mice were investigated in the CIA model, and the incidence and severity of arthritis as well as the serum levels of anti-collagen II (CII) antibodies were recorded. RESULTS: Significant effects on onset, incidence, severity, and anti-CII antibody titers were observed in female mice carrying a heterozygous congenic Cia40/Pregq2 fragment of NFR/N origin, containing one or more polymorphic genes. Congenic male mice did not show increased incidence of CIA, but males carrying a heterozygous fragment showed a significant increase in severity in comparison with wildtype B10.Q males (littermates). CONCLUSION: The Cia40/Pregq2 locus at chromosome 11 contains one or more polymorphic genes of NFR/N origin that significantly influence both incidence and severity of CIA in heterozygous congenic mice of the B10.Q strain. The major polymorphic candidate genes for the effects on CIA are Cd79b, Abca8a, and Map2k6. The congenic fragment also contains polymorphic genes that affect reproductive behavior and reproductive success. The Sox9 gene, known to influence sex reversal, is a candidate gene for the reproductive phenotype.
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| 6. |
- Liljander, Maria, et al.
(författare)
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Placental Immune Defences - Protection Against Rejection and Infection
- 2007
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Ingår i: Encyclopedia of life sciences. - : Wiley.
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The placenta must not only provide nutrients and take care of fetal waste products, it also needs to protect the fetus from maternal immunological attacks while at the same time transmitting maternal immunoglobulins to ensure protection against infectious agents.
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| 7. |
- Liljander, Maria
(författare)
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The Complex Genetics of Mouse Reproduction and Arhritis.
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- ABSTRACT Optimal breeding of mice is very important in biomedical science today. The understanding why some strains breed better and some worse enable scientists to create better in vivo models for human diseases. The aim of this thesis was to identify and characterize new genetic regions linked to reproductive performance and autoimmune inflammation in female mice. Collagen-induced arthritis (CIA) is an animal model for autoimmunity and rheumatoid arthritis (RA), and this animal model was used for the study of autoimmune reactivity in the female mice. RA is a very common autoimmune disease, which approximately affects 1-1.5% of the world population, and particularly women are affected. In Paper I the results of a genetic analyse (QTL analyse) of crossings between two inbred mouse strains, one moderate breeder (B10.Q) and one “high breeder” mouse (NFR/N) are summarized. Several new significant loci were identified for reproductive traits, such as litter size (Fecq3-4), pregnancy rate (Pregq1-4) and neonatal growth (Neogq1). In paper II, a congenic B10.Q strain carrying a fecundity locus (Fecq4) of NFR/N origin is characterized. This congenic strain showed a higher breeding performance and larger litter size than the parental B10.Q strain. In addition, the Fecq4 mice did respond stronger to the standard superovulation protocol. The possible role of some candidate genes is discussed. Paper III summarizes the QTL-results of an autoimmunity study (the CIA model) of aged multipareous female mice of the same strains and crossings as those used for reproductive studies. One new significant locus , now denoted Cia40, was identified. Finally, in paper IV, the results of studies of a congenic B10.Q mouse carrying a Cia40 locus of NFR/N origin are summarized. Females, but not males, of the Cia40 congenic strain showed altered response to CIA. The congenic Cia40 fragment also contained a reproductive locus named Pregq2, which negatively interfered with the reproductive performance of the congenic mice. Possible candidate genes have been discussed.
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| 8. |
- Roos, Åse, et al.
(författare)
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Protocol for Providing Additional Pseudo-Pregnant Recipient Mice for Embryo Transfer and Intra-Uterine Insemination by Plugging in the Middle of the Day
- 2008
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Ingår i: Scandinavian Journal of Laboratory Animal Science. - 0901-3393. ; 35:4, s. 305-310
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Tidskriftsartikel (refereegranskat)abstract
- The fact that 10% of female mice enter oestrus and allow mating in the middle of the day is an old observation that has been more or less forgotten. We here show that this old knowledge can be used to improve the efficacy of both embryo transfer and insemination protocols. The present technical paper shows that rapid re-arrangements of mating cages, to achieve pseudo-pregnant recipients in the middle of the day, can be of great advantage in emergency situations. Such emergency situations occur repeatedly, i.e. when a scientist has forgotten to re-arrange her/his mating cages, and the last important male suddenly has become ill and may die within a few hours. A rapid technique for uterine artificial insemination in mice in such situations is extremely valuable. An artificial intra-uterine insemination requires only a minimum of planning, a minimum of instrumentation and a minimum of surgical training. The artificial insemination must be performed shortly after mating due to rapid constriction of the utero-tubual junction (UTJ). This means that the timing of the insemination is very important. We here show that the success rate for embryo transfers, when using recipients plugged in the middle of the day, was the same as for ordinary overnight mating protocols. In addition, it: should be noted that the success rate (frequency of pregnancies) for uterine inseminations was 55% if using F1 recipients of C57BL/6J (considerable lower if using recipients of inbred C57BL/6J), which is amazingly high, since inseminations in mice is known to be tricky to perform in a reproducible manner.
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