Cryptosporidium infections in inbred strains of mice.

Cryptosporidium, a protozoan parasite of man and animals, is an important etiological agent of diarrhea throughout the world, particularly in children and immunocompromised individuals such as AIDS patients. Unfortunately, because of the lack of both in vivo laboratory models and reliable in vitro parasite culture systems, virtually nothing is known about the immunological events occurring during disease. In order to identify reliable animal models for infection, we studied C. parvum infections in 19 different strains of mice representing 12 H-2 haplotypes: A/J, AKR/J, B10.D2/J, B10.M/J, C3H/HeJ, C57BL/65, C57BL/6J-bgJ, CBA/NJ, DBA/1J, DBA/2J, HRS/J, HTG/J, NZB/B1NJ, NZW/J, P/J, RIII/J, SJL/J, SWR/J, and WB/ReJ, and in one gerbil: Meriones unguiculatus. Fecal samples and histological sections of the intestine taken on day 7 post-Cryptosporidium inoculation indicated that only the beige mouse (C57BL/6J-bgJ) harbored significant numbers of parasites compared to the other strains. The numbers of parasites harbored in these NK cell-deficient beige mice were, however, considerably lower than those seen in neonatal mice. Adult inbred mouse strains susceptible to Cryptosporidium infections are discussed.     

Clastogenic effect of thiophosphamide in spermatogonia of inbred strains of mice

Sensitivity of spermatogonia of 11 mouse inbred strains to induction of chromosome damages by thiophosphamide (thioTEPA) was studied. Metaphase chromosome preparations were made 24 h after treatment with thioTEPA (at 2.25 mg/kg, i/p). With respect to frequency of cells with chromosome damages, strains were ranked as follows: A/Sn (17.5 + 4.4%) greater than 101/H greater than TPS greater than WR = C57BL/6 = AKR = NZB greater than CBA/Lac greater than C3H/Sn greater than MRL greater than BALB/c (5.0 + 2.2%). This distribution does not coincide with that for sensitivity of bone marrow cells, though the data support, in general, the estimations obtained earlier for strains' mutability. Comparison of the data presented with those from literature demonstrates that the sensitivity to clastogenic effect of thioTEPA (and other alkylating agents) correlates neither with spontaneous level of SCE, nor with unscheduled DNA synthesis, nor with radiosensitivity of inbred mice. The frequency of induced chromosome aberrations in spermatogonia is relatively low and spermatogonia cannot substitute bone marrow cells as a test system when assaying chemical mutagens.     

Impulsive choice in inbred strains of mice

When humans or non-humans are given a choice between receiving a sooner-smaller (SS) reinforcer, or a later-larger (LL) reinforcer, the choice of a SS reinforcer represents impulsive choice whereas the choice of a LL reinforcer represents self-controlled choice. It has been suggested that both biological and genetic factors influence impulsive/self-control choice in this paradigm. In the present study, the inbred strains of BALB/c, C57BL/6, and DBA/2 mice were given a choice to press one of two levers in an operant chamber. Depending on their choice, mice received either a smaller reinforcer (one pellet delivered after 6s) sooner (SS) or a larger reinforcer (two pellets after 6, 9, 12, 18, or 30s) later (LL). Mice preference for the larger reinforcer decreased with longer delays. More importantly, the BALB/c mice chose the SS reinforcer more often than the C57BL/6 mice under the 9- and 12-s delays, and more often than the DBA/2 mice under the 9-s delay. This indicates that the choice pattern of the BALB/c strain is more "impulsive" than the other strains and suggests that specific gene configurations influence impulsive choice in mice.     

Variations in serum calcium between strains of inbred mice.

Serum calcium concentrations of C3H/Fg, C3H/HeJFg, AKR/Fg, A/Fg, and LCS/Fg mice were compared at 4 and 7 mo of age. In the C3H/Fg and A-strain mice, calcium levels did not differ significantly between the 2 strains nor between the 2 age groups. The C3H/HeJFg, LCS/Fg, and C57BL/Fg strains formed a distinct group with similar calcium levels, but at a significantly higher level than C3H/Fg and A/Fg group. Again there was no significant difference between the 4- and 7-mo groups. The AKR/Fg strain was distinct from both groups in that higher calcium levels characteristic of the second group (C3H/HeJFg, LCS/Fg, and C57BL/Fg, were seen at 4 mo of age, but lower calcium levels similar to those of the C3H/Fg and A/Fg strains were found at 7 mo of age.     

Quiet mutations in inbred strains of mice

The year 2009 is the 100th anniversary of the founding of the first inbred strain of mouse, called DBA. During the last 100 years, inbred strains have proved their value for biomedical research and the number of such strains has mushroomed to over 450, each with different genotypic and phenotypic characteristics and useful for the study of disease and normal function. However, although inbred strains are stable, they are not fixed entities and researchers need to be aware of the phenomena of new mutations and of genetic drift, which occur within all mouse colonies. If the mutations are what we term in this review 'quiet mutations', then they might result in rather unexpected and sometimes tremendously valuable results. Here, we discuss these phenomena and look at how new genomic technologies might help us to detect 'quiet mutations' and use them to our advantage.     

The response of recombinant inbred strains of mice to bacterial lipopolysaccharides.

Fourteen recombinant inbred strains of mice have been produced by the inbreeding of the F2 generation of a cross between C57BL/6J and C3H/HeJ progenitor mice. The responses of these BXH strains to bacterial lipopolysaccharides (LPS) have been characterized. Four BXH strains are high LPS responders and nine strains are low LPS responders. One BXH strain shows intermediate responsiveness which may reflect residual heterozygosity. F1 hybrid mice from low x high responder strains were intermediate in their response to LPS suggesting additive genetic control. The LPS responses in backcross mice from the F1 x low LPS responders showed segregation consistent with LPS responsiveness being determined by a single gene. In 13/14 BXH strains, there was concordant inheritance of LPS responsiveness and the major urinary protein locus Mup-1b. The association of the expression of the Mup-1 alleles with LPS responsiveness in the BXH strains suggests that the defective LPS response gene in C3H/HeJ mice is located on chromosome 4.     

Identification of inbred strains of mice,Mus musculus. I. Genetic control of inbred strains of mice using starch gel electrophoresis

Fifteen biochemical markers were tested in 30 inbred strains of mice to control the genetic constitution of each strain. Discrepancies in pattern from Standardized Nomenclature for Inbred Strains of Mice are reported and discussed.This work was supported by Grant No. 512–2532 from the Danish Medical Research Council.     

Sex ratio of inbred strains of mice

A study of the sex ratio in mice of the inbred strains (CBA and C3H) and connection of the postimplantation embryonic mortality in mice of these strains with the sex distribution of embryos demonstrated that the sex ratio in these mice was 1:1. Literature and the author's personal data suggested that genetic features of mice of the inbred strains failed to influence significantly the sex ratio of the offspring. The postimplantation embryonic death rate in the C3H mice exceeded that in the CBA mice (14.4 and 9.3%, respectively). However, the balanced sex ratio in mice of these strains points to the absence of selective mortality of the embryos of any one sex during embryogenesis.     

Studies on pulmonary aryl hydrocarbon hydroxylase activity in inbred strains of mice.

Pulmonary and hepatic levels of aryl hydrocarbon hydroxylase (AHH) were studied in inbred strains of mice following intratracheal (i.t.) instillation of 3-methylcholanthrene (MCA). I.t. instillation of 188 mug MCA in sterile 0.2% gelatin in saline resulted in preferential induction of pulmonary AHH. After treatment with this dose of MCA, the pulmonary AHH levels of strains C57BL/6Cum, C57BL/6J, BALB/cMai, C3H/fMai, and C57L/J were observed to be induced within 24 h after treatment. Strains DBA/2Cum, AKR/J, SJL/J, DBA/2J and RF/J expressed no such increase. At a dose of 500 mug MCA, the pulmonary tissue of DBA/2 mice did express a 4-fold increase. This increase in AHH was determined to be quite different from the increase observed in C57BL/6 mice by: (1) specific activity of the enzymes, (2) genetic regulation, (3) susceptibility to inhibition by 7,8-benzoflavone, and (4) spectral properties of the associated cytochromes. It was of major importance that induction of pulmonary AHH was observed to be regulated by a single dominant gene in crosses involving the C57BL/6Cum and DBA/2Cum strains of mice. Results were discussed with the view in mind that these genetically regulated levels of AHH may play a role in susceptibility to cancers induced by polycyclic aromatic hydrocarbon carcinogens.