The most debilitating human lymphoid deficiency disease, known as severe combined immunodeficiency (SCID), impairs the differentiation of both T and B lymphocytes. Affected infants are highly susceptible to recurring infections of viruses, fungi and bacteria and invariably die within 2 yr of birth. Inheritance of this congenital syndrome may show X-linked or autosomal recessive control. To date autosomal recessive inheritance of SCID has been observed in Arabian foals which represent the only known animal model of this disease syndrome but here we report an autosomal recessive mutation in mice that severely impairs lymphopoiesis. Mice homozygous for this mutation have few if any lymphocytes; consequently they are hypogammaglobulinaemic and deficient for immune functions mediated by T and B lymphocytes. These mice, therefore, represent a new model for investigating how lymphoid differentiation may be impaired in the disease state and regulated in the normal state.

Lymphoid and myeloid cells represent distinct lineages of a common hematopoietic stem cell (1-3). This distinction is dramatically illustrated in the autosomal recessive mouse mutant, scid . t Mice homozygous for the scid mutation (scid mice) are severely deficient in B and T lymphocytes whereas other hematopoietic cell types such as erythrocytes, monocytes, granulocytes, and megakaryocytes (all members of the myeloid series) are present in normal number (4, 5). Although the scid mutation appears to affect only lymphocyte development (4-10), it is not yet clear what stage of lymphoid differentiation is impaired or arrested .Recent results suggest that the effects of the scid mutation become manifest after the commitment of lymphoid cells to the B and T cell pathways . First, early transcription of unrearranged H chain and TCR loci, which presumably signals the opening of these loci to factors responsible for gene recombination (11-16), is detectable in scid fetal liver and thymus, respectively (Schuler, W., A. Schuler, and M. J. Bosma, unpublished results) . Second, although cells with H chain (or TCR) gene rearrangements cannot be directly demonstrated in freshly harvested lymphoid tissues of adult scid mice (17), early B cell lines with H chain gene rearrangements can be recovered from Abelson murine leukemia virus-transformed scid bone marrow cells (17) and from long-term cultures of scid bone marrow cells (18). There is also indication of early T cell development as thymic lymphomas with rearranged TCR-'Y and TCR-# alleles spontaneously appear in -15% of scid mice (5,17,19). It is striking, however, that the majority of rearranged H chain and TCR alleles in transformed scid lymphocytes show abnormal J region deletions. The deletions remove all J-coding exons of a given J region and appear to result from attempted D to J or V to Jjoining; they vary in size and extend both 5' and 3' of the deleted J regions (17,19). Evidence of abnormal J-associated deletions has also been reported for rearranged H chain alleles of long-term B cell lines derived from scid bone marrow cells (18).To explain the abnormal J-associated deletions and how they might account

Dysplastic and malignant human breast tissues were grown successfully in the cleared mammary fat pads (CFP) of nude mice. The mammary fat pads were cleared while the mice were in a germfree isolator. Prepared mice were removed fron the germfree enviornment to facilitate transplantation of the human mammary tissue into their CFP and subsequently were maintained in sterile laminar flow racks.

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