Genetic differentiation within the inbred C57BL/6J mouse strain

The C57BL/6J (B6) inbred mouse strain is commonly used in biomedical researches. However, some unexpected inconsistency was reported compared with previous studies, and in most cases, it can be attributed to environmental, epigenetic or stochastic differences. The goal of this study was to investigate the genetic stability of the B6 strain maintained in different breeders. B6 mice purchased from five Chinese commercial breeders were examined, and mitochondrial D-loop sequence and 18 microsatellite loci were genotyped. There is no difference in the D-loop sequences, but variations exist in the nucleic microsatellite markers. Combining the data from MGI_4.01, a significant divergence is observed among those mice. The present study indicates that different B6 mice share the common maternal lineage and are still inbred in each breeder, but subline divergence occurs.     

Genetic drift in an outbred stock of mice.

Survey in protein polymorphism in the nucleus colony of the Him: OF 1-mouse outbred stock showed that 8 of 53 loci were variable in the stock. Allele frequencies of these eight loci (Idh-1, Mup-1, Pgm-1; Ldr-1, Gpi-1s, Hbb, Mod-1, Ce-2) changed between generations investigated. The average percentage of heterozygote animals for these loci decreased with generation. These suggested that genetic drift occurred in the breeding stock. Examination in the breeding record sheets showed that genetic drift was caused by mistakes in mating probably due to repeated personnel changes and insufficient training of the animal technicians. Mice had not been paired according to the schemes prescribed, pairing among relatives and reduction of the number of litters used for mating occurred. The increase in homozygosity showed only little effect on breeding parameters: The interval between pairing and first and second litter increased significantly.     

Primary structure of apolipoprotein A-II from inbred mouse strain BALB/c

The primary structure of apolipoprotein A-II (apoA-II) isolated from the plasma high density lipoprotein (HDL) fraction of the inbred mouse strain BALB/c is described in this work. The complete 78 amino acid protein sequence was determined by proteolytic fragmentation, gas-phase microsequence analysis, and fast atom bombardment (FAB) mass spectrometry. The apolipoprotein has a calculated molecular weight of 8,715 and a net negative charge conveyed by ten acidic and eight basic amino acid residues. There exists a 55% amino acid sequence homology between the BALB/c mouse apoA-II and human apoA-II. Unlike human plasma apoA-II, which exists as a disulfide dimer, BALB/c apoA-II lacks cysteine and is a monomer. BALB/c apoA-II contains one residue each of histidine and arginine, neither of which are found in the human A-II protein. Chou and Fasman analysis of the BALB/c apoA-II primary structure predicts approximately 68% alpha-helical potential compared with a 62% potential for human apoA-II. The alpha-helical domains are structurally amphipathic, generating a polar and an apolar face consistent with the proposed models describing apolipoprotein-phospholipid interaction.     

Development and characterization of the IOR/Hab inbred mouse strain

The IOR/Hab inbred mouse strain, developed and maintained in the National Institute of Oncology and Radiobiology, is the first inbred strain to be developed in Cuba. It has a high fertility in this tropical climate. A number of physiological characteristics such as longevity, haematological characteristics, and growth are reported. Other experiments and results concerning spontaneous tumour frequency suggest that the strain is well adapted to standard environmental conditions, and could be useful for biomedical research.     

Hydronephrosis in the inbred mouse strain DDD

The inbred mouse strain DDD was found to have an extremely high incidence of hydronephrosis (37/37 in adult males and 12/32 in adult females). The hydronephrosis was classified as open with no definite cause for obstruction. The condition was either unilateral in the right kidney or bilateral. Another feature of the hydronephrotic kidney was circulatory failure. Hydronephrosis in strain DDD mice is considered to be a useful experimental animal model with additional possible use, in investigating disturbances of renal haemodynamics and function.     

Genetic profile of the SMXA recombinant inbred mouse strains revealed with restriction landmark genomic scanning

We have applied the restriction landmark genomic scanning (RLGS) method to the SMXA recombinant inbred (RI) mouse strain set to reveal its detailed genetic profile. A total of 663 polymorphic RLGS spot loci were identified, 576 of which were assigned to chromosomes. Strain distribution patterns (SDPs) at 55 microsatellite marker loci were also obtained. As a result, the total number of loci with distinct SDPs on chromosomes increased to 400. These loci were dispersed on all chromosomes, except for the Chromosome (Chr) Y, and effectively covered the genome with an average spacing of 4 cM. The SMXA RI strain set, hereby, would be of value for genetic study. Received: 20 February 1998 / Accepted: 19 May 1998     

Allelic profile at 37 biochemical loci of two inbred strains of the house mouse derived from wild Mus musculus musculus

Two newly established inbred strains derived from Mus musculus musculus, designated PWD/Ph (F29) and PWK/Ph (F33), were examined for their alleles at 37 biochemical loci located on 12 different chromosomes. The allelic pattern showed characteristic differences from those observed in common inbred strains. The genetic distance D between PWK/Ph and PWD/Ph was 0.027, whereas the corresponding values for the genetic distances between PWK/Ph and C57BL/6J, DBA/2J, BALB/cJ and SWR/J were 0.777, 0.721, 0.721 and 0.838 respectively. New allozymes are described as being controlled by the loci Es-23, Pre-2 and Tam-1. The genetic relationship to M.m.molossinus is indicated by identical alleles at six other loci (Es-2, Es-9, Es-10, Es-11, Es-18 and Es-22).     

A new inbred strain JF1 established from Japanese fancy mouse carrying the classic piebald allele

A new inbred strain JF1 (Japanese Fancy Mouse 1) was established from a strain of fancy mouse. Morphological and genetical analysis indicated that the mouse originated from the Japanese wild mouse, Mus musculus molossinus. JF1 has characteristic coat color, black spots on the white coat, with black eyes. The mutation appeared to be linked to an old mutation piebald (s). Characterization of the causative gene for piebald, endothelin receptor type B (ednrb), demonstrated that the allele in JF1 is same as that of classic piebald allele, suggesting an identical origin of these two mutants. Possibly, classic piebald mutation was introduced from the Japanese tame mouse, which was already reported at the end of the 1700s. We showed that JF1 is a useful strain for mapping of mutant genes on laboratory strains owing to a high level of polymorphisms in microsatellite markers between JF1 and laboratory strains. The clarified genotypes of JF1 for coat color are ``aa BB CC DD ss'. Received: 30 May 1997 / Accepted: 26 August 1997     

Inheritance of hydronephrosis in the inbred mouse strain DDD

The mode of inheritance of hydronephrosis was investigated by crossing inbred DDD mice having a high incidence of hydronephrosis and C57BL/6 mice having normal kidneys. In the males, incidences of hydronephrosis in F1 animals were intermediate between the two parental strains at a rate of 32.6% in (DDD x C57BL/6)F1 and 23.4% in reciprocal F1. The same tendency was observed in F2 male animals. In BCF1 males, the number of affected mice was higher in (C57BL/6 x DDD) F1 x DDD (72.4%) than in (DDD x C57BL/6)F1 x C57BL/6 (11.1%). A few affected mice were found among the females of hybrids F1, F2 and BCF1. These results suggested that hydronephrosis in the DDD strain of mice was controlled by polygenes, and that male hormones may have some effect on the occurrence of hydronephrosis.     

NIH/Ola: a highly productive inbred strain of laboratory mouse

According to historical records the NIH/Ola strain was developed from outbred 'Swiss' mice imported into the USA by Dr C. Lynch in 1926. A comparison of biochemical markers in strain NIH/Ola and other strains such as SJL and SWR derived from the same foundation stock supports the historical records. Data on litter size, length of gestation, bodyweight to 70 days of age, and reproductive performance when housed in polygamous groups of up to 10 females per male were compared with similar data on inbred CBA/CaOla and C57BL/10ScSnOla mice. NIH/Ola inbred mice had an exceptional reproductive performance, producing about 1.8 young weaned/female/week when housed as monogamous pairs over a period of 20 weeks, compared with less than 1.0 young/female/week with the other 2 strains. NIH/Ola mice were also extremely tolerant to mating in polygamous groups of up to about 8 females per male. Mating ratios of over 2-3 females per male resulted in a marked decline in the total number of litters produced per female in C57BL/10ScSnOla and CBA/CaOla, but this reduction was not nearly so marked in NIH/Ola. It is concluded that the NIH/Ola inbred strain may be particularly useful in studies such as teratology where a high reproductive performance needs to be combined with the advantages of a fully inbred strain.     

A collaborative database of inbred mouse strain characteristics

A database and website (MPD: Mouse Phenome Database) have been developed to serve as a consolidated home for mouse strain characterization data being generated by the scientific community. Physiological, anatomical and behavioral data are being collected and integrated into a common framework for tabulation by strain and sex. Genotypic data are being collected as well. The current focus is on a set of 40 inbred strains. The MPD as of February 2004 contains approximately 500 phenotypic parameters relevant to human health, voluntarily contributed by several dozen investigators and laboratories. AVAILABILITY: www.jax.org/phenome     

Genetic polymorphisms among C57BL/6 mouse inbred strains

Mice from the inbred C57BL/6 strain have been commonly used for the generation and analysis of transgenic and knockout animal models. However, several C57BL/6 substrains exist, and these are genetically and phenotypically different. In addition, each of these substrains can be purchased from different animal providers and, in some cases, they have maintained their breeding stocks separated for a long time, allowing genetic differences to accumulate due to individual variability and genetic drift. With the aim of describing the differences in the genotype of several C57BL/6 substrains, we applied the Illumina^® Mouse Medium Density Linkage Mapping panel, with 1,449 single nucleotide polymorphisms (SNPs), to individuals from ten C57BL/6-related strains: C57BL/6JArc, C57BL/6J from The Jackson Lab, C57BL/6J from Crl, C57BL6/JRccHsd, C57BL/6JOlaHsd, C57BL/6JBomTac, B6(Cg)-Tyr ^c?2j /J, C57BL/6NCrl, C57BL/6NHsd and C57BL/6NTac. Twelve SNPs were found informative to discriminate among the mouse strains considered. Mice derived from the original C57BL/6J: C57BL/6JArc, C57BL/6J from The Jackson Lab and C57BL/6J from Crl, were indistinguishable. Similarly, all C57BL/6N substrains displayed the same genotype, whereas the additional substrains showed intermediate cases with substrain-specific polymorphisms. These results will be instrumental for the correct genetic monitoring and appropriate mouse colony handling of different transgenic and knockout mice produced in distinct C57BL/6 inbred substrains.     

Autoimmune glomerulonephritis induced in congenic mouse strain carrying telomeric region of chromosome 1 derived from MRL/MpJ

In lupus erythematosus-prone mice, including the BXSB, NZW and NZB strains, telomeric regions of chromosome 1 (Chr.1) contain major glomerulonephritis susceptibility loci such as Bxs3, Sle1, and Nba2. To assess whether strain MRL, a model for lupus erythematosus, had glomerulonephritis susceptibility loci on Chr.1, we created B6.MRLc1(82-100) congenic mice carrying MRL/MpJ Chr.1 (82-100 cM) based on the C57BL/6 background and investigated renal pathology. From 6 months of age, B6.MRLc1 (82-100) showed the onset of diseases such as splenomegaly due to proliferation of CD3- or B220-positive cells, glomerular damage, and an increased serum anti-dsDNA antibody concentration, and these were earlier and severer in females. The score for glomerular damage was higher in B6.MRLc1(82-100) mice over 12 months old than in C57BL/6 or even in wild-type MRL/MpJ. Immune-complex depositions were demonstrated on glomerular basement membrane in B6.MRLc1(82-100) by immunohistochemistry and electron microscopy. For the percentage of IgG1-positive glomeruli, B6.MRLc1 (82-100) had significantly higher values than C57BL/6. In evaluations of clinical parameters, serum levels of blood urea nitrogen and the anti-dsDNA antibody in B6.MRLc1(82-100) were significantly higher than those in C57BL/6. In conclusion, B6.MRLc1(82-100) clearly developed autoimmune-mediated glomerulonephritis, and we demonstrated that MRL Chr.1 contained a novel glomerulonephritis susceptibility locus. We named this locus Mag (MRL autoimmune glomerulonephritis) and it provided new insights into the genetic basis and pathogenesis of lupus nephritis.     

Mx1 causes resistance against influenza A viruses in the Mus spretus-derived inbred mouse strain SPRET/Ei

Inbred SPRET/Ei mice, derived from Mus spretus, were found to be extremely resistant to infection with a mouse adapted influenza A virus. The resistance was strongly linked to distal chromosome 16, where the interferon-inducible Mx1 gene is located. This gene encodes for the Mx1 protein which stimulates innate immunity to Orthomyxoviruses. The Mx1 gene is defective in most inbred mouse strains, but PCR revealed that SPRET/Ei carries a functional allele. The Mx1 proteins of M. spretus and A2G, the other major resistant strain derived from Mus musculus, share 95.7% identity. We were interested whether the sequence variations between the two Mx1 alleles have functional significance. To address this, we used congenic mouse strains containing the Mx1 gene from M. spretus or A2G in a C57BL/6 background. Using a highly pathogenic influenza virus strain, we found that the B6.spretus-Mx1 congenic mice were better protected against infection than the B6.A2G-Mx1 mice. This effect may be due to different Mx1 induction levels, as was shown by RT-PCR and Western blot. We conclude that SPRET/Ei is a novel Mx1-positive inbred strain useful to study the biology of Mx1.