# SCID MICE AND THE CONTROL OF LYMPHOCYTE DIFFERENTIATION

> **NIH NIH R01** · RESEARCH INST OF FOX CHASE CAN CTR · 1992 · $332,939

## Abstract

DESCRIPTION (Adapted from the applicant's abstract):  Mice homozygous for
the autosomal recessive mutation, SCID (SCID mice) are severely deficient
in mature lymphocytes.  Early B and T lineage-committed cells are clearly
present in SCID lymphopoietic tissues, but are unable to differentiate into
functional B and T lymphocytes.  This developmental arrest is believed to
reflect a defect in the system responsible for the recombination of V
(variable), D (diversity) and J (joining) gene elements that code for
immunoglobulin (Ig) and T cell receptor (TCR) variable regions.

This proposal deals with two levels of complexity in the manifestation of
the SCID defect.  The first concerns whether V(D)J recombination in SCID
cells is equally defective at all Ig and TCR loci.  Since the recombination
of V(D)J elements within and between different Ig and TCR loci follows an
ordered developmental pattern, the applicant will test for possible
differences in the effect of SCID (or expression of SCID) in lymphocytes
representing distinct stages of early development.  Different populations
of lymphocytes will be analyzed for VDJ recombinase activity and V(D)J
recombination, with emphasis on the frequency of recombination and the
structure of the recombination junctions at different loci.

The second level of complexity concerns the leaky SCID phenotype.  This
refers to SCID mice that develop a few clones of functional B and T cells
and produce detectable serum Ig (Ig+); interestingly, leaky SCID mice with
B or T cells only have not been observed.  Dr. Bosma will test whether SCID
leakiness reflects a low frequency of somatic reversion at the SCID locus,
and also possibly, a low frequency of normal Ig and TCR gene rearrangement
mediated by the defective SCID recombinase activity.  He will also test to
what extent the invariable presence of T cells in serum Ig+ SCID mice
reflects T cell dependent growth requirements of B cells and/or somatic
reversion before the commitment to the B and T cell lineages.  These aims
will involve testing various cell lines from leaky SCID mice for reversion
to normal x-irradiation sensitivity (increased radiosensitivity is a
property of SCID cells), analyzing a large sample of B cell hybridomas
and/or plasmacytomas from old leaky SCID mice for normal (or abnormal)
rearrangement at the non-productive Ig alleles, and constructing athymic
nude-SCID mice and chimeric SCID mice.

The experiments outlined in this proposal should tell us more about the
effect of SCID on early lymphocyte development.  This is important for
understanding the genetic control of both normal and abnormal lymphocyte
differentiation.

## Key facts

- **NIH application ID:** 3125430
- **Project number:** 5R01AI013323-17
- **Recipient organization:** RESEARCH INST OF FOX CHASE CAN CTR
- **SAM.gov UEI:** FF1XVJMDYVR1
- **Principal Investigator:** MELVIN J BOSMA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $332,939
- **Award type:** 5
- **Project period:** 1976-05-01 → 1994-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125430

## Citation

> US National Institutes of Health, RePORTER application 3125430, SCID MICE AND THE CONTROL OF LYMPHOCYTE DIFFERENTIATION (5R01AI013323-17). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125430. Licensed CC0.

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